Psychobiology and Behavioral Strategies

The Sensory Psychobiology of Thirst

and Salt Appetite
ALAN KIM JOHNSON
Departments of Psychology, Integrative Physiology, and Pharmacology, and the Cardiovascular Center, University
of Iowa, Iowa City, IA

ABSTRACT
JOHNSON, A. K. The Sensory Psychobiology of Thirst and Salt Appetite. Med. Sci. Sports Exerc., Vol. 39, No. 8, pp. 1388–1400,
2007. Thirst and the hunger for sodium containing fluids and food (i.e., sodium appetite) are the consequences of the generation of
unique central nervous system states. Altered body fluid homeostasis produces sensory and perceptional changes that arise from signals
generated in the body that serve as indices of body fluid balance and distribution. These signaling mechanisms activate networks of
brain neurons that use specific neurochemicals to communicate between cells and process information. The brain integrates information
derived from various bodily sources so that thirst and sodium appetite are in a true sense the synthetic products of the nervous system.
In recent years much has been learned about the stimuli and receptor systems involved in signaling the brain to reflect the status of
bodily fluids and about the central neural substrates that process such inputs to generate thirst and sodium appetite. Knowledge about
the sensory nature of thirst and sodium appetite provides a basis for understanding the biological constraints under which thirst and
sodium appetite operate. This information is important for appreciating the extent to which thirst and sodium appetite motivational
states and behaviors can be relied on to maintain and repair disruptions of body fluid homeostasis. Key Words: ANGIOTENSIN II,
BARORECEPTORS, SENSORY CIRCUMVENTRICULAR ORGANS, EXERCISE-INDUCED HYPONATREMIA, HEAT INJURY

T
he perceptions of the thirst for water or a hunger for
specific minerals or macronutrients that result from
homeostatic deficits are the result of unique patterns
APPLIED SCIENCES
or the hunger for a particular substance, the brain receives
inputs from multiple sources that are related to the phy-
siological status of the body. This information is conveyed

of neural activity in the central nervous system (CNS). A
useful heuristic for understanding the biological under-
pinnings of states of thirst and various hungers is to con-
sider them to be similar to the perceptions generated by
sensory modalities such as vision, audition, olfaction, taste,
or the somatic senses (i.e., the classic senses). The neuro-
biology underlying thirst and related appetites is similar to
that of many sensory systems. However, unlike primary
sensory systems, thirst and specific hungers do not employ
unique sensory organs (eyes, ears, tongue, nose, and skin)
or a single type of dedicated receptor (rods, cones, taste
buds, hair cells) sensing the information necessary to gen-
erate the central states associated with the respective per-
ception. To produce the neural states associated with thirst
Address for correspondence: Alan Kim Johnson, Department of Psychol-
ogy, University of Iowa, 11 Seashore Hall E., Iowa City, IA 52242-1407;
E-mail: alan-johnson@uiowa.edu.
Submitted for publication December 2006.
Accepted for publication April 2007.
0195-9131/07/3908-1388/0
MEDICINE & SCIENCE IN SPORTS & EXERCISEÒ
Copyright Ó 2007 by the American College of Sports Medicine
DOI: 10.1249/mss.0b013e3180686de8
to the brain in the form of various chemical and neural
signals over multiple modalities or input pathways and then
is processed by the brain in an extensive neural network. In
effect, thirst and specific hungers are the synthetic products
of the CNS—they are created in the brain.
This review will discuss the biological nature of the
psychological states of thirst and salt appetite from the
perspective of the signals that generate them and the brain
neuronal and chemical systems responsible for creating
them. By considering thirst and similar motivated states
from the perspective of sensory and perceptual systems, it is
easier to appreciate that these behavioral controls of f luid
homeostasis operate under unique sets of biological con-
straints. Understanding the sensory and perceptual neuro-
biology of thirst and specific hungers allows an appreciation
of the probable limits of these processes and the restrictions
they have in restoring homeostasis under conditions of en-
vironmental and physical challenges.
TOTAL BODY WATER AND BODY FLUID
COMPARTMENTS
Fluid homeostasis requires mechanisms that maintain
overall sodium and water balance as well as the appropriate
distributions of these substances within the intracellular

1388

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
(ICF) and extracellular fluid (ECF) compartments of the
body. Consistency of the f luid matrix of organisms is
achieved by multiple control systems with physiological
(i.e., autonomic nervous system; hormonal) and behavioral
effectors that are coordinated by the CNS. The level of ac-
tivation of each of these mediators participates in the process
of maintaining body f luid homeostasis and the patterned
output of each response system is adjusted by the brain.
When separate sources of sodium and water are available, it
is possible to establish rates of sodium and water intake and
loss that are largely independent of one another.
Although the importance of water for maintaining f luid
homeostasis seems obvious, the contribution of sodium (or
related extracellular ions and molecules) to overall fluid
balance and distribution in the body may not be so apparent.
Sodium ions do not readily cross cell membranes and are
the key to determining the partitioning of water between the
ICF and the ECF compartments. That is, the sodium con-
centration of the ECF, in large part, determines the osmotic
gradients and forces that move water in and out of cells.
Animals drink water and ingest impermeable ions and
molecules intermittently. Between the postabsorptive phase,
a time when the hydromineral milieu is theoretically closest
to balance and the conclusion of the next drinking episode,
physiological and behavioral control systems work together
to optimize the distribution of available fluid resources and
to restore lost body water and sodium. When animals are
challenged by physiological (e.g., exercise), environmental
(e.g., increased ambient temperature), or pathophysiological
(e.g., emesis; diarrhea) conditions, afferent, neural, and
humoral signals directed to the CNS are generated and
serve as independent indices ref lecting the degree of f luid
loss from the ICF and ECF compartments (Fig. 1).
FIGURE 1—Gain and loss of water and sodium.
BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Body fluid balance is determined by interacting physio-
logical and behavioral effector systems. Behavioral mech-
anisms participate in the intake of sodium and water, and
hormonal and autonomic mediators establish the rate of loss
of these substances from the body. Both autonomic and en-
docrine mechanisms target the kidney and the sweat and
salivary glands to adjust the rates of sodium and water loss
from the body. In the kidney, the antidiuretic hormone,
vasopressin, is a well-def ined endocrine factor acting on
renal collecting ducts to increase water permeability and
water reabsorption. Aldosterone, a mineralocorticoid, acts
on renal tubules to promote sodium reabsorption. These
actions of hormones are complemented by renal tubule
sympathetic innervation that, when activated, increases the
reabsorption of sodium and water.
Hormonal and autonomic mechanisms act on the kidneys
and on sweat and salivary glands to reduce the rate of
sodium and water loss in the face of accruing fluid deficits.
However, despite renal- and endocrine-targeted defenses, it
is only by engaging motivational mechanisms for the
acquisition and consumption of water (thirst) and of sodium
(sodium or salt appetite) that restoration of sodium and
water lost to the environment can be attained.
SIGNALS REFLECTING DEHYDRATION OF BODY
FLUID COMPARTMENTS GENERATE THIRST
AND SODIUM APPETITE
In classic studies in dogs conducted in the 1930s, Gilman
(34) demonstrated that intravenous infusions of hypertonic
saline, but not hypertonic urea, induce thirst. These findings
APPLIED SCIENCES
indicated that substances excluded from cells generate an
effective osmotic pressure and, thereby, produce drinking
for the simple reason that they dehydrate the ICF compart-
ment. The additional discovery that water intake was
evoked after experimental procedures in animals that
allowed investigators to selectively deplete either ICF or
ECF led to the formulation of the so-called double depletion
hypothesis of thirst in the early 1970s (23,31).
Hypovolemia, the depletion of ECF produced by exper-
imental procedures that generate a localized edema or
remove isotonic fluid from the body (e.g., hemorrhage or
intraperitoneal dialysis), is also an effective condition for
inducing thirst. For example, Fitzsimons (30) produced
drinking in rats by intraperitoneal injections of large
molecular weight substances (hyperoncotic colloids, such
as polyethylene glycol and gum acacia) that reverse the
normal Starling forces present at the capillaries. Increased
oncotic pressure in the extracellular space at the injection
site of such colloids progressively sequesters isotonic ECF
to dehydrate interstitial f luid and reduce blood volume.
With hemorrhage, intraperitoneal dialysis or hyperoncotic
colloid–induced dehydration, the osmotic equilibrium
across cell membranes is not affected. Therefore there is
no movement of water out of the cellular compartment and
hence no reduction of ICF.
Medicine & Science in Sports & Exercised 1389
 Although thirst can be induced by selective dehydration
of either ECF or ICF (i.e., the double depletion hypothesis),
under the majority of physiological conditions thirst arises
as a result of a simultaneous depletion of the two fluid
compartments. Conjoint dehydration of the ICF and ECF by
coadministered hypertonic saline and polyethylene glycol
produces a total water intake that equals the sum of what
either dipsogenic treatment would produce when adminis-
tered independently (13).
Under physiological or pathophysiological conditions,
various hydration challenges generate different degrees of
dehydration of the ICF and ECF compartments. For exam-
ple, transpiration of water through the skin or loss by evapo-
ration from the respiratory system or oral mucosa results
in a depletion of only water and, therefore, a pure dehydra-
tion of the ICF compartment; loss of hypotonic fluid as
sweat or saliva produces loss of both ECF and ICF; fluid
depletion as a result of bleeding (e.g., hemorrhage due to
tissue damage; menstruation) produces a selective ECF loss
(i.e., hypovolemia).
Disproportionate dehydration in one body compartment
can become translated into a loss from the other compart-
ment. For example, an initial loss of hypotonic f luid results
in a relative hypernatremia that, in turn, dehydrates the in-
tracellular compartment. Ultimately, further changes to ap-
portion the distribution of dehydration to each of the body
fluid compartments can occur as a result of renal mecha-
nisms, because the kidney has the capacity to excrete either
hypotonic or hypertonic urine.
Total water loss can be differentially shared by the ICF or
ECF compartments over time and under different physiolog-
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ning 6–9 h after polyethylene glycol–induced hypovolemia.
However, if the hypovolemic animals are given access to
isotonic saline rather than water, they continue to ingest the
salty fluid at high rates (69). This indicates that sodium, in
addition to water, is required to correct hypovolemia.
In fact, Stricker_s experiments (68,69) model what had
been described in man by Adolph (1) as voluntary de-
hydration. Later, the term involuntary dehydration was
suggested to be more appropriate to describe this phenom-
enon (35). Dehydrated humans with access only to water
stop drinking before the fluid deficit is repaired. Hypovo-
lemic rats will not only restore fluid balance by ingesting
isotonic saline but will consume nonpreferred, unpalatable
concentrations of hypertonic saline if they are offered in
conjunction with water (68,70,71) (Fig. 2). A significant
increase in the intake of a concentrated, normally rejected or
unpreferred solution of NaCl is a commonly employed
operational definition of sodium appetite (i.e., salt appetite).
The experimental study of sodium appetite dates from Curt
Richter_s (58) pioneering demonstration that adrenalectomy
in the rat results in the ingestion of significant volumes of
sodium solution. Adrenalectomy removes the body_s pri-
mary source of aldosterone and therefore causes a loss of
sodium in the urine, saliva, and feces. This absence of
sodium-retaining hormone causes compensatory sodium
ingestion to replace the lost sodium. Numerous other

ical tasks or environmental conditions. Classic demonstra-

tions of thirst being maintained after the administration of
hypertonic saline while water was withheld were made by
Adolph and colleagues (2) and Holmes and Gregersen
(36,37). After delays of 3–8 h, rats and dogs drank amounts
of water that were similar to those under experimental
conditions where they were given immediate access to water.
During the time when water was not accessible, sufficient
amounts of solute were excreted so that plasma osmolarity
was nearly normalized. In other words, by excreting Na+,
the animals exchanged the prevailing stimulus for thirst, an
ICF depletion, for an ECF dehydration.
Not only are the processes underlying water intake
induced by depletion of ICF versus ECF compartments dif-
ferent, so are the mechanisms of satiety. Fitzsimons (29)
demonstrated that nephrectomized rats infused with effec-
tive osmotic agents drink sufficient water to restore body
fluids to isotonicity. Anephric rats that cannot use renal
mechanisms to excrete Na+ behave as near-perfect osmom-
eters. In contrast, animals with pure hypovolemia do not
FIGURE 2—Mean hourly cumulative intakes, in total licks, showing
restore fluid balance by ingesting only water. Studying rats the pattern of water and 0.5 M NaCl solution intake by rats during the
made hypovolemic by subcutaneous administration of 24-h period after subcutaneous injection of 30% polyethylene glycol
polyethylene glycol, Stricker (68,69) demonstrated that rats in isotonic saline to induce hypovolemia (N = 5). (Reprinted from
Stricker, E. M., K. S. Gannon, and J. C. Smith. Thirst and salt appetite
do not maintain high rates of water intake in the face of induced by hypovolemia in rats: analysis of drinking behavior. Physiol.
persisting hypovolemia. That is, water intake slows begin- Behav. 51:27–37, 1992. Used with permission.)

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TABLE 1. Experimental manipulations commonly employed to induce salt appetite.
Primary salt appetite
Absolute sodium deficit induced by depletion
Dietary sodium restriction
Perspiration (exercise in the heat with restoration of water loss
without sodium)
Adrenalectomy
Peritoneal dialysis
Natriuretic treatment
Salivary sodium loss
Relative sodium deficit
Sequestration of extracellular fluid (e.g., polyethylene glycol)
Pharmacological simulation
Combined natriuretic–hypotensive drug (e.g., furosemide + captopril;
furosemide + minoxidil)
Aldosterone or deoxycorticosteroid acetate (DOCA)
Intracerebroventricular angiotensin or renin treatment
Intracerebroventricular angiotensin + priming with low-dose aldosterone
>2-adrenoceptor antagonist treatment (yohimbine)
experimental manipulations have been shown to enhance
the ingestion of concentrated solutions of NaCl in animals.
These treatments range from pharmacological doses of
aldosterone to the induction of sodium depletion by any of
several methods including dietary restriction (Table 1). It
is interesting to note that the majority of the experimental
manipulations used to induce sodium appetite require sub-
stantial periods of time to elapse, often on the order of
several hours to days, before a significant increase in con-
centrated NaCl becomes apparent. This is in contrast to
the shorter latencies for the onset of thirst (i.e., signifi-
cant water intake) after experimental depletion of the ICF
or ECF compartments.
The first time animals are made sodium def icient, they will
consume large quantities of NaCl on being given access to
salty fluids even though they have had no previous ex-
perience with such solutions (25). Display of this appetite
for sodium by naBve animals provides evidence that the
appetitive and consummatory behaviors associated with
sodium appetite are innate. However, this native behavior is
also modifiable as a result of prior experience. A single
sodium depletion, regardless of whether the animal does or
does not orally consume sodium, produces an enhanced
NaCl intake response on subsequent tests in response to
sodium depletion (26,62). The phenomenon of enhanced
NaCl intake after an initial treatment can be mimicked by
administration of exogenous angiotensin II (ANG II) and
aldosterone (62).
Many of the treatments that induce sodium appetite also
induce water intake; however, the converse does not hold.
For example, depletion of ICF with hypertonic saline induces
water intake but little, if any, intake of hypertonic NaCl (57).
Such observations led Peck (57) to suggest that ICF
depletion–induced water drinking and ECF depletion–
induced water drinking and sodium ingestion may be the
reflection of different types of thirst. In experimental
animals, it is impossible to test whether a thirst induced
by ICF depletion is qualitatively different than a thirst
induced by ECF depletion. It is probably best to use
objective operational definitions of (the state of) thirst as
measured by a significant increase in water intake and (the
BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
state of) sodium appetite as indexed by a significant
increase in hypertonic saline solution intake. Although in
principle both thirst and sodium appetite can exist simulta-
neously, under common experimental conditions only one
behavior can be expressed and measured at a time. The
investigation of the patterns of water and NaCl intake after
dehydration proves instructive and has increased the under-
standing of the neural and endocrine mechanisms that
control the generation of the hydromineral-related ingestive
behaviors involved in maintaining body fluid homeostasis.
Stricker and colleagues (70,71) characterized the time
course of the onset of thirst (water intake) and sodium
appetite (NaCl intake) after the induction of hypovolemia
induced by subcutaneous polyethylene glycol treatment.
The general result from such studies indicates that although
significant increases in water intake are apparent within an
hour or two after polyethylene glycol treatment, it usually
takes on the order of 5–7 h before significant increases in
the consumption of concentrated (i.e., 2 or 5%) NaCl
solutions are observed (Fig. 2). The reasons for this relative
delay in onset are probably because of the need for an
increase in one or more facilitory factors or a decrease in
inhibitory mechanisms. Such processes may be related to
the degree or duration of hypovolemia, the consequences of
first drinking water (i.e., to produce a decrease in
osmolarity of ECF), increased hormonal levels (e.g., ANG
II; aldosterone), the development of hypotension, or some
combination of these factors (44,45,72).
After NaCl intake commences, animals alternate between
drinking water and ingesting concentrated sodium solution
(Fig. 2). By adjusting the volumes of water and hypertonic
APPLIED SCIENCES
saline consumed over time, rats end up consuming the
equivalent of a near-isotonic (0.9–1.2%) mixture (70).
Thus, two distant behaviors driven by two different moti-
vational states provide the optimal strategy for the hypo-
volemic animal to correct an ECF def icit. Sodium appetite
as demonstrated by a significant increase in hypertonic
NaCl solution intake has been demonstrated in many avian
and mammalian species. This paradigm has not been
applied to study the recovery from dehydration in humans.
The classical studies of human sodium deficiency were
conducted by McCance (50), who used himself and three
volunteers as subjects. Severe sodium deficits were induced
by low-sodium diet and episodes of sweating. During the
sodium-depleted state, which was maintained for 11 d, the
subjects reported excessive fatigue, lethargy, and a general
feeling of exhaustion. The sense of taste was generally
affected. Food and cigarettes were described as tasteless.
The subjects differed in their desire for sodium. One subject
described a distinct longing for salt and often went to sleep
thinking about it, but McCance reported having no specific
craving for sodium.
More recently, better-controlled experiments employing
more objective methods have been used to assess sodium
appetite in humans after sodium depletion. Beauchamp and
colleagues (6) studied the effects of a very-low-sodium diet
Medicine & Science in Sports & Exercised 1391
 and diuretic treatment on taste in normal subjects for a 10 d
period. As assessed after 5 and 10 d of depletion, thresholds
for the taste of salt decreased in the majority of subjects, and
the preference judgments for salt in foods tended to be
greater. It is interesting to note that during the depletion
period, despite increased plasma aldosterone and renin
activity, supine and upright blood pressure were slightly
decreased. Together, the data are interpreted as indicating
that sodium depletion in humans produces moderate sensory
(salt taste) changes and increased preference for salty foods.
The time course and development of sodium appetite in
humans rehydrating without sodium replacement has been
studied by Takamata and colleagues (74). These investiga-
tors induced H2O and Na+ depletion by light exercise (eight
APPLIED SCIENCES
FIGURE 3—Subjective palatability rating as a function of tasted NaCl
solution molarity in subjects initially dehydrated and then rehydrated
(beginning at 0-h rehydration) with only water. Concentrations of
tasted solutions are expressed on a logarithmic scale. Data are means T
SE (n = 7). * Significant difference from control, P G 0.05. Reprinted
from Takamata, A., G. W. Mack, C. M. Gillen, and E. R. Nadel.
Sodium appetite, thirst, and body fluid regulation in humans during
rehydration without sodium replacement. Am. J. Physiol. Regul. Integr.
Comp. Physiol. 266:R1493–R1502, 1994. Used with permission.
1392 Official Journal of the American College of Sports Medicine
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bouts during 7 h), which was followed by a rehydration
period providing only ad libitum water. After a delay of
several hours, the subjects began to express a significant
increase in palatability ratings for hypertonic saline sol-
utions. The increased acceptance over the hypertensive
range of solutions became most apparent 17–23 h after the
start of rehydration (Fig. 3). It is unclear whether factors
such as reduced plasma osmolarity or the presence of
hypotension were responsible for increasing perceived
sodium palatability during the course of rehydration.
VISCERAL AND BRAIN SENSORY RECEPTORS
DETECT THE STATUS OF BODY FLUID BALANCE
Both chemo- and mechanoreceptors sense the status of
body f luids. These receptors are located in the systemic viscera
and in the brain. Increasing the osmolarity of brain ECF by
injection of hypertonic cerebrospinal fluid into the cerebral
ventricles activates vasopressin release, sympathetic outf low,
and thirst. These physiological and behavioral responses are
biologically consistent with one another and cooperatively
produce an increase in total body water and a tendency to
elevate blood pressure. Such responses have been proposed
to be mediated by neuron-like cells, which sense their own
volume and are referred to as osmoreceptors (80,81).
Although there are many osmosensitive regions in the
CNS and body, including the hepatoportal region, one of
the key areas housing osmoreceptors for thirst and vaso-
pressin release lies within the periventricular tissue sur-
rounding the anteroventral portion of the third cerebral
ventricle (AV3V) (40,44,45). AV3V-associated structures
that play particularly important roles in osmoreception and/
or processing are the ventral median preoptic nucleus and
the organum vasculosum of the lamina terminals (OVLT).
The OVLT along with two other anatomically and func-
tionally unique structures, the subfornical organ (SFO) and
the area postrema (AP), are referred to as sensory circum-
ventricular organs (43). Sensory circumventricular organs
like the other similar structures are devoid of a blood–brain
barrier, but whereas most of the other circumventricular
organs function as sites of secretion, sensory circumven-
tricular organs have been implicated as structures sensing
humoral signals in blood or interstitial fluid. Cells with
stretch-sensitive ion channels have been identified electro-
physiologically within the OVLT (7) and are, therefore,
primary candidates as osmoreceptors.
A second key humoral signal that acts on the brain to
effect responses consistent with restoration or expansion of
body fluids and elevation of blood pressure is circulating
ANG II. Systemic administration of ANG II elevates
arterial blood pressure, releases vasopressin, and increases
the ingestion of water and sodium (44,45). These ingestive,
pressor, and secretory responses are also produced by ANG
II administered directly into the brain ventricles.
There are several regions in the CNS sensitive to ANG II.
The SFO in particular has been implicated in the activation
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of thirst, salt appetite and vasopressin release by circulating
ANG II (44,45). It has been hypothesized that the brain
renin–angiotensin system (i.e., a system with its compo-
nents synthesized de novo in the brain) is coupled with the
systemic (i.e., renal) renin–angiotensin system through the
SFO (38). Circulating angiotensin in the mode of a
hormone acts on sensory circumventricular organs to
activate brain neural pathways. Brain interneurons, in turn,
release angiotensin from their axon terminals, which then
functions like a traditional neurotransmitter (38,39,43).
Considerable attention has been paid to the contribution
of brain steroid receptors in the generation of sodium
appetite (24). Mineralocorticoids (e.g., aldosterone), when
given in pharmacological doses (82) or in more physio-
logical concentrations in conjunction with ANG II (32),
produce significant NaCl ingestion. The facilitory interac-
tion that can be achieved with systemic injections of very
low doses of aldosterone and small amounts of ANG II
injected into the brain has been referred to as the synergy
hypothesis for sodium appetite (24).
Mechanoreceptors identif ied as key for sensing blood
volume and arterial blood pressure are located in the
periphery. The great veins and atria (i.e., the low-pressure
side of the circulation) contain what are often referred to
as cardiopulmonary receptors (a misleading terminology,
because there are many different types of visceral sensory
receptors associated with the heart and lungs) that are
responsive to stretch. These sensors generate afferent nerve
traffic to the CNS in proportion to distention of the walls of
the great veins (e.g., superior vena cava) and atria. Similar
stretch receptors located in the aortic arch and carotid sinus
sense changes in arterial blood pressure. Output from these
receptors change in proportion to arterial blood pressure.
Information from low- and high-pressure baroreceptors as
well as from cardiac ventricular mechano-/chemoreceptors
reaches the brain by the IXth and Xth cranial nerves. When
blood pressure and/or blood volume falls below a ‘‘normal’’
set point, nerve activity declines and results in triggering the
reflex release of vasopressin, increased sympathetic outflow,
and, ultimately, thirst and sodium appetite. A moderate
reduction in blood pressure (induced by antihypertensive
agents) in the presence of hypovolemia synergizes to rapidly
generate sodium appetite and thirst, which are dependent on
a renin–angiotensin system that is intrinsic to the brain (76).
Maintaining blood pressure or cutting neural afferents from
high-pressure baroreceptors (sinoaortic denervation) blocks
this type of experimentally induced sodium appetite (77).
Blood pressure at hypertensive or normotensive levels is
likely to inhibit thirst and sodium appetite (44,45,59).
A BRAIN NEURAL NETWORK PROCESSES FLUID
BALANCE-RELATED INPUT TO MAINTAIN
BODY FLUID HOMEOSTASIS
The generation of the appetitive and consummatory
behaviors necessary to acquire and ingest water and sodium
BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
requires the integration of information derived from several
types of sensory systems. Visceral afferent signals must
communicate the body’s need for water and sodium to the
brain. In the process of seeking water and sodium, sensory
systems are engaged for identif ication of potential sources
in the external environment. When in contact with food and
fluids, gustatory mechanisms assess the taste qualities of the
ingesta to identify the commodity as an acceptable source
of water or sodium for consumption.
The VIIth, IXth, and Xth cranial nerves carrying taste and
visceral information enter the brain stem and synapse
primarily in the nucleus of the tractus solitarius (NTS).
Axons from cells in the NTS, in turn, project to other brain
nuclei. Similarly, input detected by sensory circumventric-
ular organs (SFO, OVLT, AP) is also carried into the brain
by nerves emanating from these structures. Many of the
brain pathways and regions carrying and processing input
from the systemic chemo- and mechanoreceptors and from
sensory circumventricular organs have been defined and
characterized by anatomical, neurochemical, and functional
techniques. The result has been the identif ication of a neu-
ral network that both carries and integrates information
critical for the regulation of fluid balance. Pathways and
information initially processed by the AP and NTS ascend
the neuraxis to meet information deriving from the SFO and
OVLT. Between the forebrain and hindbrain portals of
input, there are several nodes (brain nuclei) where informa-
tion from such various sources converges.
In principle, activity in any pathway and nucleus in the
brain can influence information handling (processing and
storage) within the neural network that controls the
APPLIED SCIENCES
effectors maintaining body fluid and cardiovascular homeo-
stasis. However, there are brain areas that have been found
to be especially critical in these processes. Most notable
among these brain regions are 1) the sensory circum-
ventricular organs (i.e., SFO, OVLT, and AP), 2) the NTS,
3) caudal and rostral ventrolateral medulla, 4) parabrachial
nucleus (PBN), 5) the median preoptic nucleus, 6)
parvocellular hypothalamic paraventricular nucleus, 7)
magnocellular paraventricular nucleus, 8) supraoptic
nucleus, 9) amygdala (particularly the central and medial
nuclei of the amygdala), 10) bed nucleus of the stria
terminalis, 11) lateral hypothalamus, 12) ventrolateral
medulla, and 13) the spinal cord intermediolateral cell
column (42,44,45). Reciprocal pathways connect most of
these structures with one another and provide feedforward
and feedback neural circuits that are necessary for achieving
the processing of information within the CNS. Information
handling and processing within this hydromineral–neural
network is necessary for both acute and chronic adjustments
involved in regulating body f luid balance and distribution
(e.g., hemodynamics). There are many neurotransmitter
systems associated with this body f luid–related brain
network. Two of the most important of the central neuro-
chemical mediators are norepinephrine and angiotensin.
Pathways containing these putative neurotransmitters are
Medicine & Science in Sports & Exercised 1393
 distributed throughout the CNS and are associated with most,
if not all, of the key structures involved in f luid balance and
cardiovascular control. Evidence indicates that these two
brain neurochemical systems are important for mobilizing
effector systems that expand ECF volume (39,44,45).
In addition to facilitory mechanisms, there are inhibitory
counterparts represented in the central f luid regulatory
network that retard overexpansion of the ECF compartment.
Evidence indicates that such inhibition may involve brain
oxytocin (72), serotonin (44,45,51–53), tachykinins (49),
cholecystokinin (54), and bombesin (15,16).
In recent years, signif icant progress has been made in
several laboratories in identifying forebrain and hindbrain
components of the hydromineral neural network subserving
thirst and sodium appetite as well as those for physio-
logical control systems (i.e., sympathetic and endocrine).
Systemically derived information has immediate access to
the forebrain via actions on rostral sensory circumventric-
ular organs associated with the lamina terminalis (Fig. 4).
The lamina terminalis is comprised of a layer of ependymal
cells that during early development covers the rostral end of
the neural tube. In mature animals, this sheet of cells forms
the rostral wall of the third ventricle, and four midline
structures, the SFO, the median preoptic nucleus, the
anterior commissure and the OVLT, lie adjacent to the
lamina terminalis. The SFO is situated in the dorsal aspect
of the third ventricle and the OVLT is located along the
ventral portion of the lamina terminalis, both of these sense
plasma ANG II levels and extracellular osmolarity.
APPLIED SCIENCES
Both the SFO and OVLT project to the median preoptic
nucleus that lies between them and is located inside the blood–
brain barrier. The median preoptic nucleus is an important
integrative node, processing both angiotensin-derived and
osmotic information. Neural activity in the median preoptic
nucleus partly determines the degree and pattern of activation
of the physiological and behavioral control systems for body
fluid homeostasis (41). Numerous studies have implicated the
SFO (66,75), the ventral median preoptic nucleus (27,28),
and the combined ventral median preoptic nucleus and
OVLT region in the control of thirst and sodium appetite
(5,8,19,40). Several pathways descend from lamina termi-
nalis structures to innervate key forebrain nuclei that have
been implicated in thirst (e.g., lateral hypothalamic/periforn-
ical area), sodium appetite (central nucleus of the amygdala),
anterior pituitary hormone control (parvocellular paraven-
tricular nucleus; PVN), posterior pituitary function (magno-
cellular PVN and supraoptic nuclei), and sympathetic
outflow (parvocellular PVN) (Fig. 4).
In contrast to the forebrain facilitory actions of ANG II,
hyperosmolarity, and mineralocorticoid binding, other sig-
nals act through a hindbrain system to keep water and
sodium intake in check. This inhibitory system involves the
neural circuitry of the AP, the medial portion of the NTS
(AP/mNTS), and the lateral PBN (44,45).
Ablation of the AP/mNTS dramatically increases the
intake of concentrated sodium chloride solution both in
chronic (11) and acute (21) experimental tests. An
important component of a neural pathway projecting from

FIGURE 4—Organization of structures of the lamina terminalis region (midsagittal representation) and projections from the lamina terminalis to
key forebrain area involved in the control of the endocrine, autonomic, and behavioral systems that participate in body f luid regulation. The
subfornical organ, organum vasculosum of the lamina terminalis (OVLT), the median preoptic nucleus, and anterior commissure are adjacent to the
lamina terminalis and can be referred to as the structures of the lamina terminalis. CRF, corticotropin-releasing factor; ACTH, adrenocorticotropic
hormone; PVN, paraventricular nucleus.

1394 Official Journal of the American College of Sports Medicine http://www.acsm-msse.org

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
the AP/mNTS to the lateral PBN (14,64,79) contains
serotonin (48). Bilateral injections of serotonin antagonists
directly into the lateral PBN markedly enhance both thirst
and sodium appetite induced by many dipsogenic and
natriorexigenic challenges (44,45,53). Several recent stud-
ies have also implicated the actions of cholecystokinin,
GABA, corticotropin-releasing hormone, and norepineph-
rine in the lateral PBN on sodium and water intake
(3,9,17,18,54). In many respects the LPBN seems to be a
switch to determine whether water intake versus sodium
intake becomes the predominant behavior used to correct
body f luid deficits.
The lateral PBN (Fig. 5) is an integrative region involved
in processing viscerally derived inhibitory input. An
example of the importance of the lateral PBN in the
inhibition of behaviors related to volume expansion has
FIGURE 5—A schematic depicting a hindbrain system involved in the
inhibitory control of thirst and sodium appetite. The key hindbrain
structures implicated are the area postrema (AP), nucleus of the
solitary tract (NTS), and the lateral parabrachial nucleus (LPBN). To
simplify the diagram, pathways are only presented unilaterally.
Lesions of the AP and LPBN produce overdrinking to thirst-inducing
stimuli that simulate hypovolemia. In the presence of thirst- or salt
appetite-inducing stimuli, bilateral injections of the nonselective
serotonergic receptor antagonist, methysergide, into the LPBN causes
profound overdrinking and sodium intake. The LPBN, in turn,
projects to forebrain structures such as the central nucleus of the
amygdala (CeA), bed nucleus of the stria terminalis (BNST), and
median preoptic nucleus (not shown). Therefore, the AP–LPBN has
been proposed to be a hindbrain circuit that guards against hyper-
volemia or expanded blood volume. VII, IX, X, input of cranial nerves.
BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
recently been demonstrated. Inflating a small balloon at the
junction of the vena cava and right atrium in rats inhibits
thirst (46) and sodium appetite (78). The expansion of such
a balloon in rats with lesions of the lateral PBN is no longer
effective in inhibiting isoproterenol-induced drinking (56).
This observation is consistent with other findings (22,54)
indicating that the lateral PBN is a key brain region
controlling behaviors that inf luence ECF volume. Informa-
tion processed within the lateral PBN is carried deeper into
the neural network for hydromineral balance where it
interacts with other types of input, particularly those from
sites receiving humorally derived signals from the lamina
terminalis (Fig. 5).
Although much of the neural circuitry of thirst and sodium
appetite is contained within the brain stem and limbic
system, we probably become aware of our thirst and hunger
for salty substances because of activation of parts of the
cerebral cortex. This is a reasonable expectation (hypothesis)
because the highest levels of information processing for
perception in other sensory systems occur at various cortical
loci. In recent studies using positron emission tomography,
Derek Denton and his colleagues (20) have identified in
human volunteers several brain regions that are activated in
conjunction with a strong sensation of thirst produced by
intravenous infusions of hypertonic saline. Among the brain
regions showing changes in activity associated with the
desire to drink were the anterior and posterior portions of
the cingulate cortex. This is a brain region associated with
motivational and affective processes.
APPLIED SCIENCES
EXERCISE, CONDITIONING, AND BIOLOGICAL
CONSTRAINTS ON THIRST AND
SODIUM APPETITE
There is a substantial body of experimental evidence
indicating that maintaining adequate hydration is critical for
health and well-being (4,63). The excessive loss of water
and sodium in extreme environments or while engaging in
athletics not only impairs performance but also increases
the likelihood of thermal injury (73). Significant water and
sodium losses can occur very quickly in both fit and
untrained individuals, especially if exercising in a hot
environment. The speed of onset of severe dehydration
under extreme conditions can exceed the onset of thirst and
sodium appetite. Thirst drive resulting from dehydration
may occur on the order of minutes to tens of minutes, but
the onset of sodium appetite is likely to require many hours
before a significant hunger develops (70,74). Impaired
thirst and sodium appetite mechanisms that accompany the
normal aging process (47) are likely to only complicate this
problem. Although behavioral mechanisms of drinking and
salt ingestion can act in concert with the kidney to restore
body f luid homeostasis over the long-term, the mobilization
of thirst- and especially sodium appetite-related behaviors
do not have sufficiently rapid response times to prevent
immediate consequences of severe water and sodium losses.
Medicine & Science in Sports & Exercised 1395
 Beyond concerns of the extended lag times for the onset
of thirst and sodium appetite that constrain the efficiency in
converting exercise-induced fluid deficits into corrective
behaviors, there are exercise-induced fluid shifts and
hemodynamic changes that are likely to also compromise
the reliability of rehydration-related behaviors for def icit
correction. The nature of circulatory changes and of fluid
movement among lymphatic, intravascular and interstitial
spaces, as well as the movement between ICF and ECF
compartments (60) that accompany exercise, needs to be
considered. Unfortunately, little is known about how
changes in fluid distribution produced either as a result of
chronic exercise and physical conditioning (e.g., expansion
of blood volume (12)) or by acute exercise will alter af-
ferent signaling mechanisms. At present, one can only
speculate about the effects of exercise and conditioning on
thirst and sodium appetite based on hydromineral-related
hormonal or autonomic responses under such conditions.
For example, Nose and colleagues (55) have demonstrated
that during graded exercise the threshold for the release of
vasopressin is increased. Therefore, one might also suspect
that increased inhibition of water or sodium intake would
accompany exercise. Perhaps increases in arterial pressure
and venous return associated with exercise would contribute
to such inhibition, but this has not been studied in relation
to thirst or sodium appetite.
The degree of loading of cardiopulmonary baroreceptors
have been demonstrated to affect both thirst and vasopressin
secretion. Head-out water immersion produces a shift of
blood volume toward the thorax stretching the large
capacitance vessels and the atria produces a reduction of
APPLIED SCIENCES
thirst, water intake, and vasopressin secretion in dehydrated
subjects (61,67). Interestingly, this inhibitory effect on thirst
and vasopressin release does not occur in older subjects
(67). It has been suggested by Stachenfeld and colleagues
(67) that the attenuated inhibitory mechanisms may be due
to impaired cardiopulmonary reflexes (10). From this per-
spective, one might consider the possibility that thirst in
athletes with cardiac hypertrophy and diminished cardio-
vascular reflex function (33) may have impaired fluid-
related behavior and endocrine responses to altered stretch
of vessels containing cardiopulmonary receptors.
Despite the limitations imposed by the sensory nature of
thirst and sodium appetite, it is important to recognize that
the cognitive capacities of humans provide a means of
compensating for limitations inherent in intrinsic biological
motivational processes. That is, cognitive mechanisms can
activate behaviors to drink or consume salt and override an
absence of thirst and sodium appetite. However, f luid intake
resulting from only cognitive processes without the activa-
tion of thirst- or sodium appetite–related mechanisms may
lead to inappropriate water and salt intake. In this context it is
important to note that not only is hypohydration caused by
inadequate thirst and sodium appetite a concern, but under
conditions of extreme athletic challenges there is also the risk
of cognitively overdriven f luid intake. The result can be
1396 Official Journal of the American College of Sports Medicine
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
exercise-induced hyponatremia, a dilutional hyponatremia
associated with positive f luid balance. This disorder is
produced in part by the excess secretion of antidiuretic
hormone (i.e., arginine vasopressin (65)) and can be life
threatening. Excessive ingestion of fluid prompted only by
a cognitively based formula clearly carries a risk of
untoward consequences produced by hyponatremia.
By viewing thirst and sodium appetite from the perspec-
tive of sensory psychobiology, it becomes easier to appre-
ciate that there are biological limits on the functional
capacities of motivational systems. That is, just as there are
limitations in the classic senses in terms of thresholds for
detection and discrimination, there are restrictions as to how
fast and how reliably the receptors and neural systems
subserving thirst and salt appetite can sense and respond to
changes in hydrational status. Just as we employ micro-
scopes, telescopes, pressure transducers, audio amplif iers,
and other instrumentation to enhance and resolve physical
stimuli, which normally serve to excite the classic senses, it
is not unreasonable to expect that it may be necessary to
employ instrumentation (scales, osmometers, sodium ana-
lyzers) to assess hydrational status under extreme and
rapidly changing conditions.
SUMMARY AND CONCLUSIONS
Maintaining body fluid and cardiovascular homeostasis
requires the integrative capacity of the CNS. A thirst for
water or a hunger for sodium are perceptions that result
from synthetic processes carried out in the brain. The CNS
receives visceral and somatic sensory inputs and integrates
this information. Through this process, calculated decisions
are made by the brain and the best pattern of reflexes and
behaviors are generated to optimize available fluid distri-
bution between body compartments and to restore hydro-
mineral balance. The key behaviors that are necessary for
the maintenance and recovery of normal fluid balance are
those that lead to the acquisition and consumption of both
water (thirst) and sodium (sodium appetite).
Figure 6 summarizes several of the major points
identifying the afferent stimuli and central circuitry relevant
to the behavioral controls of ECF volume. To the left of the
box, one of the primary sites for osmoreception related to
thirst and vasopressin release is identified as a component
of the lamina terminalis. To the right and above the large
box representing the brain are the neural and humoral inputs
that communicate the status of body fluid and cardiovas-
cular homeostasis to the CNS. Under a range of physio-
logical conditions, circulating ANG II is a participant in the
generation of thirst and sodium appetite and its actions are
complemented by additional visceral afferent inputs. ANG
II accesses the CNS through brain circumventricular organs,
particularly the SFO.
Systemic input carried over nerves from the viscera
originates in vascular baroreceptors. Hypovolemia and/or
hypotension result in input to the CNS that enhances
http://www.acsm-msse.org
FIGURE 6—Diagram depicting neural and hormonal inputs into the brain and the central neural pathways that mediate the sensory integration of
signals for generating drinking (thirst) and sodium ingestion (salt appetite). Both inhibitory and excitatory inputs from the periphery are derived from
arterial and cardiopulmonary baroreceptors as well as other visceral receptors (e.g., gastric, hepatic/portal, renal). Information carried in afferent
nerves projects mainly to the nucleus of the tractus solitarius (NTS). Angiotensin (ANG) acts in the form of ANG II on angiotensin type 1 receptors in the
subfornical organ (SFO). Osmoreception takes place in structures along the ventral lamina terminalis (OVLT; median preoptic nucleus (MePO)).
Hormonal information to the SFO is subsequently carried in descending pathways, some of which are likely to use ANG in the mode of a
neurotransmitter, to forebrain structures such as those in the tissue surrounding the anteroventral third ventricle. Ascending information to the
forebrain is carried in projections from noradrenergic cell groups in the hindbrain which are activated by arterial and cardiopulmonary receptor input
under conditions of hypotension and/or hypovolemia (not shown). ANG and noradrenergic inputs act synergistically in forebrain nuclei. A hindbrain
inhibitory pathway originating in the area postrema (AP) and medial NTS ascends to the lateral parabrachial nucleus. This projection uses serotonin
(5-HT) as a neurotransmitter and prevents excessive sodium and water intake thereby limiting excess expansion of blood volume. Inhibitory input is
likely to ascend the neuraxis either directly or indirectly to interact with forebrain structures. FAC, facilitation; INH, inhibition; AMYG, amygdala;
BNST, bed nucleus of the stria terminalis; LPBN, lateral parabrachial nucleus; SNS, sympathetic nervous system; JG, juxtaglomerular.

activity in central facilitory systems. Conversely, hyper-
volemia and/or hypertension activate inhibitory mecha-
nisms. Other types of facilitory and inhibitory input from
the viscerally derived gastrointestinal tract, splanchnic and
hepatoportal circulation and the kidneys also are likely to
feed into the neural network for fluid balance.
In the brain, angiotensin acting within the SFO has been
proposed to activate several descending projections to key
forebrain structures such as the median preoptic nucleus,
hypothalamic perifornical area, central nucleus of the
amygdala, supraoptic nucleus, and paraventricular nucleus.
Some of the fibers from the SFO and other lamina
terminalis structures are angiotensinergic. These pathways
and their termination sites are associated with the control of
the behaviors and reflexes that maintain body fluid balance
and cardiovascular homeostasis (Fig. 4). Ascending facili-
tory and inhibitory inputs project into many of these same
forebrain regions. For example, norepinephrine is released
at key forebrain sites and acts to reinforce the actions of
angiotensin to generate thirst and sodium appetite.
Several recent studies have described the role of
inhibitory influences arising in the periphery and activating
neural circuitry in the hindbrain. Central structures impli-
cated in this inhibitory system are the AP/mNTS and the
lateral PBN. The inhibitory actions of serotonin within the
APPLIED SCIENCES
lateral PBN have been associated with a hindbrain
projection from the AP/mNTS to the lateral PBN that has
been proposed to protect from overexpansion of the ECF
compartment.
The integration of information derived from facilitory
and inhibitory humoral and visceral neural inputs is
conducted within many different nodes (nuclei) in a sensory
network that regulates hydromineral balance. The outputs of
this network both controls motor-pattern generators respon-
sible for the appetitive and consummatory behaviors and
give rise to a sensory experience perceived as thirst and
sodium appetite.
Taking into consideration the basic neurobiology of the
brain systems maintaining fluid balance, it becomes
apparent that generation of thirst or sodium appetite results
from a set of neural computations based on a complex of
facilitory and inhibitory afferent signals. Phenomena such
as voluntary (or involuntary) dehydration arise from failure
to consume adequate sodium in conjunction with water.
It is important to recognize that there are limits to the
operating capabilities of the behavioral controls of body
fluid homeostasis. Like any sensory system, there are
thresholds for detection and discrimination of the pattern
of stimuli that are perceived as thirst or sodium appetite. It
should be recognized that cognitive instructions derived

BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE Medicine & Science in Sports & Exercised 1397

Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
 from the cortex can supplement the mechanisms of thirst
and sodium appetite which arise from phylogenetically old
parts of the nervous system. Appropriately informed, cog-
nitive mechanisms can be useful in maintaining adequate
hydration. However, the strength of cognitive mechanisms
can also lead to either inappropriate hypo- or hyperhydra-
tion, conditions with their own attendant risks.
Under extreme conditions all sensory systems fail.
Technology to enhance sensory capacity is appropriate in
many circumstances. As more is learned about the nature of
REFERENCES
1. ADOLPH, E. F. Physiology of Man in the Desert, New York, NY:
Interscience Publishers, pp. 254–270, 1947.
2. ADOLPH, E. F., J. P. BARKER, and P. A. HOY. Multiple factors in
thirst. Am. J. Physiol. 178:538–562, 1954.
3. ANDRADE, C. A., S. P. BARBOSA, L. A. DE LUCA JR., and J. V.
MENANI. Activation of alpha2-adrenergic receptors into the lateral
parabrachial nucleus enhances NaCl intake in rats. Neuroscience
129:25–34, 2004.
4. BARR, S. I. Effects of dehydration on exercise performance. Can.
J. Appl. Physiol. 24:164–172, 1999.
5. BEALER, S. L., and A. K. JOHNSON. Sodium consumption following
lesions surrounding the anteroventral third ventricle. Brain Res.
Bull. 4:287–290, 1979.
6. BEAUCHAMP, G. K., M. BERTINO, D. BURKE, and K. ENGELMAN.
Experimental sodium depletion and salt taste in normal human
volunteers. Am. J. Clin. Nutr. 51:881–889, 1990.
7. BOURQUE, C. W., S. H. OLIET, and D. RICHARD. Osmoreceptors,
osmoreception, and osmoregulation. Front. Neuroendocrinol.
15:231–274, 1994.
8. BUGGY, J., and A. K. JOHNSON. Preoptic-hypothalamic periven-
tricular lesions: thirst deficits and hypernatremia. Am. J. Physiol.
APPLIED SCIENCES
Regul. Integr. Comp. Physiol. 233:R44–R52, 1977.
9. CALLERA, J. C., L. B. OLIVEIRA, S. P. BARBOSA, D. S COLOMBARI,
L. A. DE LUCA JR., and J. V. MENANI. GABA(A) receptor
activation in the lateral parabrachial nucleus induces water and
hypertonic NaCl intake. Neuroscience 134:725–735, 2005.
10. CLEROUX, J., C. GIANNATTASIO, G. BOLLA, et al. Decreased
cardiopulmonary ref lexes with aging in normotensive humans.
Am. J. Physiol. Heart Circ. Physiol. 257:H961–H968, 1989.
11. CONTRERAS, R. J., and P. W. STETSON. Changes in salt intake
lesions of the area postrema and the nucleus of the solitary tract in
rats. Brain Res. 211:355–366, 1981.
12. CONVERTINO, V. A. Blood volume: its adaptation to endurance
training. Med. Sci. Sports Exerc. 23:1338–1348, 1991.
13. CORBIT, J. D. Cellular dehydration and hypovolaemia are additive
in producing thirst. Nature 218:886–887, 1968.
14. CUNNINGHAM, E. T. JR., R. R. MISELIS, and P. E. SAWCHENKO. The
relationship of efferent projections from the area postrema to vagal
motor and brain stem catecholamine-containing cell groups: an
axonal transport and immunohistochemical study in the rat.
Neuroscience 58:635–648, 1994.
15. DE CARO, G., C. POLIDORI, T. G. BELTZ, and A. K. JOHNSON. Area
postrema, lateral parabrachial nucleus, and the antinatriorexic
effect of bombesin. Peptides 19:1399–1406, 1998.
16. DE CARO, G., C. POLIDORI, J. V. MENANI, and A. K. JOHNSON.
Bombesin affects the central nervous system to produce sodium
intake inhibition in rats. Physiol. Behav. 63:15–23, 1998.
17. DE CASTRO E SILVA, E., J. B. FREGONEZE, and A. K. JOHNSON.
Corticotropin-releasing hormone in the lateral parabrachial
nucleus inhibits sodium appetite in rats. Am. J. Physiol. Regul.
Integr. Comp. Physiol. 290:R1136–R1141, 2006.
1398 Official Journal of the American College of Sports Medicine
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
controls affecting thirst and sodium appetite and how these
are influenced by the environment and exercise, a body of
knowledge will be developed to provide the best strategies
for maintenance and restoration of body fluid homeostasis
for health and well-being.
The work was supported in part by grants from the National
Heart, Lung, and Blood Institute HL 14388 and HL-57472, and from
the National Institute of Diabetes and Digestive and Kidney
Diseases DK-066086.
18. DE GOBBI, J. I. F., L. A. DE LUCA JR., A. K. JOHNSON, and J. V.
MENANI. Interaction of serotonin and cholecystokinin in the lateral
parabrachial nucleus to control sodium intake. Am. J. Physiol.
Regul. Integr. Comp. Physiol. 280:R1301–R1307, 2001.
19. DE LUCA, L. A. JR., O. GALAVERNA, J. SCHULKIN, S. Z. YAO, and
A. N. EPSTEIN. The anteroventral wall of the third ventricle and the
angiotensinergic component of need-induced sodium intake in the
rat. Brain Res. Bull. 28:73–87, 1992.
20. DENTON, D., R. SHADE, F. ZAMARIPPA, et al. Neuroimaging of
genesis and satiation of thirst and an interoceptor-driven theory of
origins of primary consciousness. Proc. Natl. Acad. Sci. U. S. A.
96:5304–5309, 1999.
21. EDWARDS, G. L., T. G. BELTZ, J. D. POWER, and A. K. JOHNSON.
Rapid-onset ‘‘need-free’’ sodium appetite after lesions of the
dorsomedial medulla. Am. J. Physiol. Regul. Integr. Comp.
Physiol. 264:R1242–R1247, 1993.
22. EDWARDS, G. L., and A. K. JOHNSON. Enhanced drinking after
excitotoxic lesions of the parabrachial nucleus in the rat. Am. J.
Physiol. Regul. Integr. Comp. Physiol. 261:R1039–R1044, 1991.
23. EPSTEIN, A. N. Epilogue: retrospect and prognosis. In: The
Neuropsychology of Thirst: New Findings and Advances in
Concepts, A. N. Epstein, H. R. Kissileff, and E. Stellar (Eds.).
Washington, DC: V.H. Winston, pp. 315–332, 1973.
24. EPSTEIN, A. N. Mineralocorticoids and cerebral angiotensin may
act together to produce sodium appetite. Peptides 3:493–494,
1982.
25. EPSTEIN, A. N., and E. STELLAR. The control of salt preference in
the adrenalectomized rat. J. Comp. Physiol. Psychol. 48:167–172,
1955.
26. FALK, J. L. Serial sodium depletion and NaCl solution. Physiol.
Behav. 1:75–77, 1966.
27. FITTS, D. A. Effects of lesions of the ventral ventral median
preoptic nucleus or subfornical organ on drinking and salt appetite
after deoxycorticosterone acetate or yohimbine. Behav. Neurosci.
105:721–726, 1991.
28. FITTS, D. A., D. S. TJEPKES, and R. O. BRIGHT. Salt appetite and
lesions of the ventral part of the ventral median preoptic nucleus.
Behav. Neurosci. 104:818–827, 1990.
29. FITZSIMONS, J. T. Drinking by nephrectomized rats injected with
various substances. J. Physiol. (Lond.) 155:563–579, 1961.
30. FITZSIMONS, J. T. Drinking by rats depleted of body fluid without
increase in osmotic pressure. J. Physiol. (Lond.) 159:297–309,
1961.
31. FITZSIMONS, J. T. Some historical perspectives in the physiology of
thirst. In: The Neuropsychology of Thirst: New Findings and
Advances in Concepts, A. N. Epstein, H. R. Kissileff, and E.
Stellar (Eds.). Washington, DC: V.H. Winston, pp. 3–33, 1973.
32. FLUHARTY, S. J., and A. N. EPSTEIN. Sodium appetite elicited by
intracerebroventricular infusion of angiotensin II in the rat: II.
Synergistic interaction with systemic mineralocorticoids. Behav.
Neurosci. 97:746–758, 1983.
http://www.acsm-msse.org
33. GIANNATTASIO, C., G. SERAVALLE, G. B. BOLLA, et al. Cardiopulmo-
nary receptor reflexes in normotensive athletes with cardiac
hypertrophy. Circulation 82:1222–1229, 1990.
34. GILMAN, A. The relation between blood osmotic pressure, fluid
distribution and voluntary water intake. Am. J. Physiol. 120:
323–328, 1937.
35. GREENLEAF, J. E. Problem: thirst, drinking behavior, and involun-
tary dehydration. Med. Sci. Sports Exerc. 24:645–656, 1992.
36. HOLMES, J. H., and M. I. GREGERSEN. Observations on drinking
induced by hypertonic solutions. Am. J. Physiol. 162:326–337,
1950.
37. HOLMES, J. H., and M. I. GREGERSEN. Role of sodium and chloride
in thirst. Am. J. Physiol. 162:338–347, 1950.
38. JOHNSON, A. K. The periventricular anteroventral third ventricle
(AV3V): its relationship with the subfornical organ and neural
systems involved in maintaining body fluid homeostasis. Brain
Res. Bull. 15:595–601, 1985.
39. JOHNSON, A. K. Brain mechanisms in the control of body fluid
homeostasis. In: Perspectives in Exercise Science and Sports
Medicine, Volume 3: Fluid Homeostasis During Exercise, C. V.
Gisolfi and D. R. Lamb (Eds.). Carmel, IN: Benchmark Press, pp.
347–419, 1990.
40. JOHNSON, A. K., and J. BUGGY. Periventricular preoptic-hypothal-
amus is vital for thirst and normal water economy. Am. J. Physiol.
Regul. Integr. Comp. Physiol. 234:R122–R129, 1978.
41. JOHNSON, A. K., J. T. CUNNINGHAM, and R. L. THUNHORST.
Integrative role of the lamina terminalis in the regulation of
cardiovascular and body fluid homeostasis. Clin. Exp. Pharmacol.
Physiol. 23:183–191, 1996.
42. JOHNSON, A. K., J. DE OLMOS, C. V. PASTUSKOVAS, A. M. ZARDETTO-
SMITH, and L. VIVAS. The extended amygdala and salt appetite.
Ann. N. Y. Acad. Sci. 877:258–280, 1999.
43. JOHNSON, A. K., and P. M. GROSS. Sensory circumventricular
organs and brain homeostatic pathways. FASEB J. 7:678–686,
1993.
44. JOHNSON, A. K., and R. L. THUNHORST. The neuroendocrinol-
ogy of thirst and salt appetite: visceral sensory signals and mecha-
nisms of central integration. Front. Neuroendocrinol. 18:292–353,
1997.
45. JOHNSON, A. K., and R. L. THUNHORST. The neuroendocrinology,
neurochemistry and molecular biology of thirst and salt appetite.
In: Handbook of Neurochemistry and Molecular Neurobiology:
Behavioral Neurochemistry, Neuroendocrinology and Molecular
Neurobiology, 3rd ed., A. Lajtha and J. D. Blaustein (Eds.). New
York, NY: Springer, pp. 641–688, 2007.
46. KAUFMAN, S. Role of right atrial receptors in the control of
drinking in the rat. J. Physiol. (Lond.) 349:389–396, 1984.
47. KENNEY, W. L., and P. CHIU. Influence of age on thirst and fluid
intake. Med. Sci. Sports Exerc. 33:1524–1532, 2001.
48. LAN0A, A. J., and D. VAN DER KOOY. A serotonin-containing
pathway from the area postrema to the parabrachial nucleus in the
rat. Neuroscience 14:1117–1126, 1985.
49. MASSI, M., L. GENTILI, M. PERFUMI, G. DE CARO, and J. SCHULKIN.
Inhibition of salt appetite in the rat following injection of
tachykinins into the medial amygdala. Brain Res. 513:1–7,
1990.
50. MCCANCE, R. A. Medical problems in mineral metabolism: III.
Experimental human salt deficiency. Lancet 1:823–830, 1936.
51. MENANI, J. V., L. A. DE LUCA JR., and A. K. JOHNSON. Lateral
parabrachial nucleus serotonergic mechanisms and salt appetite
induced by sodium depletion. Am. J. Physiol. Regul. Integr.
Comp. Physiol. 274:R555–R560, 1998.
52. MENANI, J. V., L. A. DE LUCA JR., R. L. THUNHORST, and A. K.
JOHNSON. Hindbrain serotonin and the rapid induction of sodium
appetite. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279:
R126–R131, 2000.
53. MENANI, J. V., and A. K. JOHNSON. Lateral parabrachial serotoner-
BEHAVIORAL MECHANISMS IN BODY FLUID BALANCE
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
gic mechanisms: angiotensin-induced pressor and drinking
responses. Am. J. Physiol. Regul. Integr. Comp. Physiol. 269:
R1044–R1049, 1995.
54. MENANI, J. V., and A. K. JOHNSON. Cholecystokinin actions in
the parabrachial nucleus: effects on thirst and salt appetite.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 275:R1431–R1437,
1998.
55. NOSE, H., A. TAKAMATA, G. W. MACK, et al. Water and electrolyte
balance in the vascular space during graded exercise in humans.
J. Appl. Physiol. 70:2757–2762, 1991.
56. OHMAN, L. E., and A. K. JOHNSON. Role of lateral parabrachial
nucleus in the inhibition of water intake produced by right atrial
stretch. Brain Res. 695:275–278, 1995.
57. PECK, J. W. Discussion: Thirst(s) resulting from bodily water
imbalances. In: The Neuropsychology of Thirst: New Findings
and Advances in Concepts, A. N. Epstein, H. R. Kissileff,
and E. Stellar (Eds.). Washington, DC: V.H. Winston & Sons,
pp. 99–112, 1973.
58. RICHTER, C. P. Increased salt appetite in adrenalectomized rats.
Am. J. Physiol. 115:155–161, 1936.
59. ROBINSON, M. M., and M. D. EVERED. Pressor action of intra-
venous angiotensin II reduces drinking response in rats. Am. J.
Physiol. Regul. Integr. Comp. Physiol. 252:R754–R759, 1987.
60. ROWELL, L. B. Human Cardiovascular Control. New York, NY:
Oxford University Press, 1993.
61. SAGAWA, S., K. MIKI, F. TAJIMA, et al. Effect of dehydration on
thirst and drinking during immersion in men. J. Appl. Physiol.
72:128–134, 1992.
62. SAKAI, R. R., W. B. FINE, A. N. EPSTEIN, and S. P. FRANKMANN. Salt
appetite is enhanced by one prior episode of sodium depletion in
the rat. Behav. Neurosci. 101:724–731, 1987.
63. SAWKA, M. N., and E. F. COYLE. Influence of body water and
blood volume on thermoregulation and exercise performance in
the heat. Exerc. Sport Sci. Rev. 27:167–218, 1999.
64. SHAPIRO, R. E., and R. R. MISELIS. The central neural connections
of the area postrema of the rat. J. Comp. Neurol. 234:344–364,
1985.
APPLIED SCIENCES
65. SIEGEL, A. J. Exercise-associated hyponatremia: role of cytokines.
Am. J. Med. 119:S74–S78, 2006.
66. SIMPSON, J. B., and A. ROUTTENBERG. Subfornical organ: site of
drinking elicitation by angiotensin II. Science 181:1172–1175,
1973.
67. STACHENFELD, N. S., L. DIPIETRO, E. R. NADEL, and G. W. MACK.
Mechanisms of attenuated thirst in aging: role of central volume
receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 272:
R148–R157, 1997.
68. STRICKER, E. M. Osmoregulation and volume regulation in rats:
inhibition of hypovolemic thirst by water. Am. J. Physiol. 217:
98–105, 1969.
69. STRICKER, E. M. Inhibition of thirst in rats following hypovolemia
and/or caval ligation. Physiol. Behav. 6:293–298, 1971.
70. STRICKER, E. M., K. S. GANNON, and J. C. SMITH. Thirst and salt
appetite induced by hypovolemia in rats: analysis of drinking
behavior. Physiol. Behav. 51:27–37, 1992.
71. STRICKER, E. M., and J. E. JALOWIEC. Restoration of intravascular
fluid volume following acute hypovolemia in rats. Am. J. Physiol.
218:191–196, 1970.
72. STRICKER, E. M., and J. G. VERBALIS. Sodium appetite. In:
Handbook of Behavioral Neurobiology, Vol. 10, Neurobiology of
Food and Fluid Intake, E. M. Stricker (Ed.). New York, NY:
Plenum Press, pp. 387–419, 1990.
73. SUTTON, J. R. Clinical implications of fluid imbalance. In:
Perspectives in Exercise Science and Sports Medicine, Volume
3: Fluid Homeostasis During Exercise, C. V. Gisolfi and D. R.
Lamb (Eds.). Carmel, IN: Benchmark, pp. 425–444, 1990.
74. TAKAMATA, A., G. W. MACK, C. M. GILLEN, and E. R. NADEL.
Sodium appetite, thirst, and body fluid regulation in humans
Medicine & Science in Sports & Exercised 1399
 during rehydration without sodium replacement. Am. J. Physiol.
Regul. Integr. Comp. Physiol. 266:R1493–R1502, 1994.
75. THUNHORST, R. L., T. G. BELTZ, and A. K. JOHNSON. Effects of 79.
subfornical organ lesions on acutely induced thirst and salt appetite.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 277:R56–R65, 1999.
76. THUNHORST, R. L., and A. K. JOHNSON. Renin-angiotensin, arterial 80.
blood pressure, and salt appetite in rats. Am. J. Physiol. 266:
R458–R465, 1994.
77. THUNHORST, R. L., S. J. LEWIS, and A. K. JOHNSON. Effects of 81.
sinoaortic baroreceptor denervation on depletion-induced salt
appetite. Am. J. Physiol. 267:R1043–R1049, 1994. 82.
78. TOTH, E., J. STELFOX, and S. KAUFMAN. Cardiac control of salt
APPLIED SCIENCES
1400 Official Journal of the American College of Sports Medicine
Copyright @ 2007 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
appetite. Am. J. Physiol. Regul. Integr. Comp. Physiol. 252:
R925–R929, 1987.
VAN DER KOOY, D., and L. Y. KODA. Organization of the projec-
tions of a circumventricular organ: the area postrema in the rat.
J. Comp. Neurol. 219:328–338, 1983.
VERNEY, E. B. The antidiuretic hormone and the factor which
determines its release. Proc. R. Soc. Lond. B Biol. Sci. 135:27–106,
1947.
WOLF, A. V. Osmometric analysis of thirst in man and dog. Am. J.
Physiol. 161:75–86, 1950.
WOLF, G. Sodium appetite elicited by aldosterone. Psychon. Sci.
I:211–212, 1964.
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