Journal of Affective Disorders 62 (2001) 113–121

www.elsevier.com / locate / jad

The effects of inositol treatment in animal models of psychiatric

disorders

Haim Einat, R.H. Belmaker*

Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel

Abstract

Clinical trials indicate that inositol may be effective in the treatment of patients with depression, panic disorder and
obsessive compulsive disorder (OCD), but not in the treatment of patients with schizophrenia, Alzheimer’s disease, ADHD
or autism. This spectrum of clinical action parallels that of serotonin selective reuptake inhibitors (SSRIs), but inositol is a
precursor in the phosphatidylinositol cycle, a second messenger system distal to the receptor for 5HT-2. To study its
mechanism of therapeutic action there is a need to test inositol’s activity in animal models of psychopathology. In rats,
chronic inositol was demonstrated to increase activity levels, reduce immobility time in the forced swim test and in the
reserpine-induced hypoactivity models of depression, and reduce anxiety-like behaviors in the elevated plus-maze. The
reduction in anxiety-like behaviors appears to be related to baseline levels of activity. Inositol treatment was not observed to
have any effect on amphetamine-induced hyperactivity, apomorphine-induced stereotypy, or on the performance of memory
tasks by monkeys. Clinical controlled trials of inositol in patients with depression, panic disorder, and OCD were small, and
positive psychoactive effects in animals clearly strengthen the case for further clinical trials and potential for general
therapeutic use in humans.  2001 Elsevier Science B.V. All rights reserved.

Keywords: Inositol; Animal models; Depression; Anxiety; Second messengers

1. Introduction disorders (Rodgers, 1997; Willner, 1991b), it is clear

The development of novel drugs for the treatment
of psychiatric disorder and the understanding of their
mechanism of action is dependent on our ability to
test pharmaceutical compounds in appropriate animal
models of these diseases (Abramson and Seligman,
1977; Willner, 1991a). Beyond the thoroughly dis-
cussed problematics of animal models for psychiatric
*Corresponding author. Tel.: 1 972-7-6401-602; fax: 1 972-7-
6401-621.
E-mail address: belmaker@bgumail.bgu.ac.il (R.H. Belmaker).
that their use is still the best option to screen
potential novel drug treatments in psychiatry.
Inositol is an endogenous polyol that has emerged
during the last few years as a new possible treatment
in psychiatry (Levine, 1997). Inositol is the pre-
cursor of the PI cycle in the cell and as such is
necessary for the production of two second messen-
gers: Inositol triphosphate 3 (IP3 ) and DAG. Unlike
most psychotropic drugs, inositol is probably not
acting directly in the synapse but in second mes-
senger systems distal to receptors.
Inositol does not readily enter the brain and only

0165-0327 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved.
PII: S0165-0327( 00 )00355-4
114 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121
about 3% of plasma inositol crosses the blood brain
barrier (Spector, 1998). Yet, exogenously adminis-
tered oral inositol was demonstrated to increase CSF
inositol levels in chronic schizophrenic patients
(Levine et al., 1993c). In rats, acute intraperitoneal
injection of 5 g / kg resulted in increased inositol
levels in cortex, hypothalamus and hippocampus
(Patishi et al., 1996) and chronic dietary inositol (5%
in food for 3 weeks) elevated inositol levels in the
cortex and hippocampus (Kofman et al., 1998).
A possible relevence of inositol to psychiatric
disorders was first suggested by Barkai et al. (1978)
who reported that patients with affective disorders
had reduced CSF inositol levels. Although these
findings were not replicated (Levine et al., 1996),
recent studies reported reduced inositol level in
frontal cortex of post mortem brains of patients with
bipolar disorder and victims of suicide (Shimon et
al., 1997). Furthermore, clinical studies with inositol
demonstrated that it may have therapeutic value in
the treatment of depression (Levine, 1997; Levine et
al., 1993a, 1995a), depression accompanying post-
traumatic stress disorder (Kaplan et al., 1996), panic
disorder (Benjamin et al., 1995), and obsessive-
compulsive disorder (OCD; Fux et al., 1996). In
contrast, no therapeutic effects were found in schizo-
phrenic patients (Levine et al., 1993b; Levine et al.,
1994), Alzheimer patients (Barak et al., 1996),
individuals with Attention Deficit Hyperactivity Dis-
order (Levine et al., 1995b), or autistic patients
(Levine et al., 1997). This clinical spectrum parallels
that of the anti-depressant serotonin selective uptake
inhibitors (SSRI’s).
The present paper reviews a variety of studies of
the effects of inositol treatment on animal behavior.
Two studies tested the effects on normal behavior
and the others tested effects on animal models of
psychopathology. The goal of these studies was to
confirm psychoactive effects for this compound
which had been studied in only a small number of
patients, and to define at least one robust effect of
inositol in an animal model that could be used for
detailed neurochemical studies of mechanism and
dose–response relationships.
1.1. Depression related studies
The effects of inositol treatment were tested in
three different conditions related to depression:
activity levels in normal rats; reserpine induced
hypoactivity; the Porsolt forced swimming test.
1.1.1. Activity levels studies
Two studies examined the effects of inositol on
activity level in rats, the first one tested the effects of
acute intraperitoneal inositol treatment (Kofman et
al., 1993) and the second examined the effects of
chronic oral inositol administration (Kofman et al.,
1998).
For the first study, Sprague Dawley rats were
housed 4 per cage in a temperature controlled (238C)
and 12 h light dark cycle colony room, with food and
water provided ad lib. All tests were done during the
dark phase of the light dark cycle. Rats were divided
to five groups which received saline (n 5 8); glucose
1 g / kg (n 5 10); glucose 5 g / kg (n 5 10; inositol 1
g / kg (n 5 9); and inositol 5 g / kg (n 5 10). All drugs
were diluted in distilled water and administered via
intra-peritoneal injection in a volume of 2 ml / 100 g
weight. Two hours after injection, rats were placed in
automated activity monitors (Optivarimax, Colum-
bus Instruments, USA) and their behavior monitored
for horizontal and vertical activity for 20 min.
The vertical activity (number of rearings) of the
inositol 1 g / kg group was significantly higher than
of the other groups (ANOVA: F(4,42) 5 3.18, P 5
0.022; followed by Neuman–Keuls post-hoc test).
No other significant effects were found but a similar
non-significant trend was demonstrated for horizontal
activity induced by the same inositol dose (1 g / kg).
For the second study, 20 male rats were housed 5
per cage in similar conditions to the previous experi-
ments. Rats received ad lib food containing 5%
inositol or 5% glucose plus mannitol at 1:2 ratio for
3 weeks. On day 22 of treatment, rats were placed in
activity monitors for 30 min. Total ambulatory
activity as well as horizontal activity (rearing) levels
were measured and served for later analysis.
Results show that inositol treatment induced in-
creased ambulation (approximately 30% increase,
F 5 11.64, P 5 0.003) and increased rearing (ap-
proximately 60% increase, F 5 16.27, P , 0.0008)
compared with control animals.
1.1.2. Reserpine induced hypoactivity ( Einat et al.,
1999)
Two experiments were conducted to test the
effects of inositol in the reserpine induced hypoac-
 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121 115

tivity model of depression. The difference between
the two experiments was only in the dose of re-
serpine used to induce hypoactivity.
Rats (Sprague Dawley males weighing 200–250 g
at the beginning of experiment) were housed 4 per
cage, with free access to food and water, in a
temperature controlled (228C) animal colony with 12
h light dark cycle. All treatments and experimental
procedures were conducted during the light phase of
the cycle.
A treatment group (n 5 10 for each experiment)
received 14 daily inositol injections (1.2 g / kg di-
luted in deionized water to injection volume of 12
ml / kg). A control group (n 5 10 for each experi-
ment) received equivalent injections of glucose:
mannitol in a 1:2 ratio. During the last 3 days of
each experiment all rats were also given daily
subcutaneous (SC) reserpine injections. The dose of
reserpine was 0.5 mg / kg for the first experiment and
0.25 mg / kg for the second experiment. Reserpine
was diluted in deionized water, with a minimal
amount of citric acid added, to injection volume of 2
ml / kg.
Thirty minutes after the last reserpine injection,
rats were placed in automated activity monitors
(Elvicom, Israel) and their behavior monitored for
ambulatory and vertical activity for 30 min. Since
the activity monitors are not sensitive enough to
detect locally oriented activity (and therefore dif-
ferentiate between complete immobility and small
movements), manual scoring of behavior was also
performed and an experimenter scored complete
immobility periods of rats for 1 min for each 10 min
of the test session (totalling 3 min per rat). Data for
all measures (ambulatory behavior, vertical activity,
and immobility score) were analyzed utilizing a
student’s t-test.
As shown in Table 1, inositol treatment was
effective in reducing complete immobility time in
both experiments. A similar trend was also demon-
strated in the second experiment for increased am-
bulatory behavior but did not reach statistical signifi-
cance.
1.2. Forced swim test ( Einat et al., 1999)
Two experiments were conducted to test the
effects of chronic treatment with intraperitoneal
(experiment 1) or oral (experiment 2) inositol on
rats’ performance in the Porsolt forced swim test, an
established model of depression (Porsolt et al., 1978;
Borsini and Meli, 1988).
Experiment 1 was designed to test a number of
doses of inositol. Accordingly, 3 groups of rats
received 2 weeks of daily intraperitoneal inositol
injections at different doses: 0.3 g / kg (n 5 9); 0.6
g / kg (n 5 10); and 1.2 g / kg (n 5 8). All doses were
diluted in deionized water to volume of 12 ml / kg.
Control rats (n 5 10) received injections of 1.2 g / kg,
1:2 glucose: mannitol solution.
For experiment 2, rats were fed for 14 days with
inositol (10% in powdered rat chow, n 5 20) or 1:2
glucose: mannitol (10% in powdered rat chow, n 5
20). The powdered food replaced the regular food
chow in this experiment and was provided ad lib.
Since normal daily food consumption of rats is

Table 1
Effects of inositol treatment on reserpine-included hypoactivity model of depression. Significant effects are observed for the measure of
‘immobility time’ at both reserpine doses
Experiment Behavior Treatment Mean 1 std P value
Experiment 1: Immobility inositol 170.9 1 7.3 0.024
0.5 mg / kg time (s) control 177.6 1 3.5
reserpine Ambulation inositol 248.7 1 189.5 N.S.
counts control 342.7 1 651.8
Experiment 2: Immobility inositol 38 1 25.8 0.0003
0.25 mg / kg time (s) control 98 1 33.9
reserpine Ambulation inositol 981.5 1 364.9 N.S.
counts control 771.6 1 229.9
Vertical inositol 31.8 1 23 N.S.
counts control 31.1 1 28.5
116 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121

approximately 10% of body weight, it can be esti-
mated that the oral daily inositol dose in this
experiment | 2.5–3 g.
Swim exposure for both experiments was con-
ducted during days 13 and 14.
The Porsolt swim test includes two exposures to a
water tank, spaced 1 day apart (Borsini and Meli,
1988; Porsolt et al., 1978; Sanchez and Meier, 1997).
For these experiments the tank sizes were 22 cm in
diameter and 40 cm in height. The tank had a
rounded lid and contained 20 cm high fresh water at
258C. During the first exposure, rats were placed into
the tank and left there for 10 min. During the second
exposure (test session), rats were placed in the tank
and left there for 5 min during which their behavior
was videotaped.
Videotapes of the test session were scored by a
blind observer for complete immobility time, small
movements time, and vigorous struggle time. The
division of activity levels to three rather than the
traditional 2 (yes or no) levels is an elaboration of
the method that may be more appropriate to examine
the effects of different treatments (Borsini and Meli,
1988). Results were analyzed utilizing one-way
analysis of variance (ANOVA) followed by LSD
post-hoc tests for experiment 1, and by a student’s
t-test for experiment 2. Significance level was set at
P , 0.05.
Table 2 shows the results of the forced swim test
experiments. These results demonstrate that chronic
inositol treatment with intraperitoneal 1.2 g / kg dose,
but not with lower doses, significantly reduced
immobility time compared with control animals
(ANOVA: F(4) 5 3.07586, P 5 0.026; post-hoc tests:
inositol (1.2 g / kg) different than control, and in-
creased struggle time compared with controls
(ANOVA: F(4) 5 6.23, P 5 0.0005; post-hoc test
inositol (1.2 g / kg) different than control). Similar
results were obtained for rats treated chronically with
oral inositol (10% in powdered rat chow). Reduced
immobility time was observed compared with control
rats (t-test: t(38) 5 3.77286, P 5 0.0006) and strug-
gle time in the treatment group appears increased
although the difference did not reach statistical
significance (t-test: t(38) 5 1.76297, P 5 0.086).
1.3. Anxiety related studies
1.3.1. Effects of acute and chronic inositol in the
plus-maze model of anxiety ( Cohen et al., 1997 a)
The elevated plus-maze serves to model anxiety-
like behavior in rodents. It is based on a conflict

Table 2
Effects of chronic intraperitoneal and chronic oral inositol on behavior in the Porsolt forced swim test. Significant effects are observed for
‘immobility time’ and ‘struggle time’ measures after chronic intraperitoneal inositol, and for the ‘immobility time’ measure after chronic
oral inositol
Experiment Behavior Treatment Mean6std P value
Experiment 1: Immobility control 178.2 1 32.3 0.026
Chronic time (s) inositol 161 1 21.6 post hoc
intraperitoneal 0.3 g / kg inositol 1.2 g / kg
inositol inositol 168.5 1 45.2 vs. control
or control 0.6 g / kg 140.5 1 26.7
inositol
1.2 g / kg
Struggle control 36 1 27.6 0.0005
time (s) inositol 38 1 38.4 post hoc
0.3 g / kg inositol
inositol 56.5 1 47.1 1.2 g / kg
0.6 g / kg vs. control
inositol 80.3 1 47.3
1.2 g / kg

Experiment 2: Immobility control 147 1 49.8 0.0006

Chronic oral time (s) inositol 95.1 1 36.2
inositol or Struggle control 31.3 1 29 NS
control time (s) inositol 47.5 1 29.1 (0.086)
 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121
situation between the exploratory drive of rodents
and their aversion from open spaces (e.g. Rodgers
and Cole, 1994). The model is one of the most
frequently used models in psychopharmacology and
had been validated in numerous studies (for review
see File, 1992). The first attempt to examine the
effects of inositol treatment in the plus-maze was
done by Cohen et al. (1997a). In that study, the
effects of a variety of acute doses injected peripher-
ally, two doses injected acutely in intracerebroven-
tricular injection, and one dose injected chronically
and intraperitoneally were examined in the elevated
plus-maze.
Results of the dose–response study of acute
peripheral inositol treatment (0.03–2.5 g / kg) indi-
cated that a single peripheral injection of inositol
may have an anxiogenic effect compared with con-
trol solution (data not shown). However, a single
ICV injection of 5 mg inositol resulted in reduced
anxiety-like behaviors in the elevated plus-maze
(data not shown). Thus, the data regarding the acute
effects of inositol in this model are not clear. In
human studies, inositol treatment was demonstrated
to have a therapeutic effect in anxiety disorders only
after chronic treatment (Benjamin et al., 1995).
Therefore the evaluation of the effects in the model
in a chronic treatment paradigm appears to be the
most appropriate.
To examine the effects of chronic inositol, groups
of rats (n 5 10 per group) were treated with daily
intraperitoneal injections of inositol (1.25 g / kg
diluted to 10% in de-ionized water) or control
solution (1:2 glucose / mannitol at equal concentra-
tion and dilution) for 14 days. Two hours after the
last injection rats were tested in the elevated plus-
maze. As shown in Fig. 1, rats treated chronically
with inositol spent significantly more time in the
open arms of the maze and demonstrated a similar
trend in the measure of number of entries to these
arms. These measures indicate that chronic inositol
treatment has anxiolytic-like properties in the ele-
vated plus-maze model. In line with the results of
other studies (Kofman et al., 1993; Kofman et al.,
1998), the inositol group also demonstrated in-
creased activity compared with the control group as
observed by increased number of entries to both the
open and the closed arms of the maze (data not
shown). This finding could imply that the anxiolytic-
like effect is an artifact of hyperactivity but the fact
117
Fig. 1. Effects of chronic inositol (1.25 g / kg daily for 14 days) in
the elevated plus-maze model of anxiety. Time spent in open arms
and number of entries to open arms. * Represents significant
difference, P , 0.05.
that inositol significantly increased the time spent in
the open arms supports a specific anxiolytic-like
activity.
Support for the previous findings was found
recently in a study of the anxiolytic-like effect in the
elevated plus-maze of inositol and one of its isomers,
epi-inositol (Einat et al., 1998a). Chronic intraperi-
toneal inositol treatment was demonstrated again to
produce anxiolytic-like effects in the elevated plus-
maze as shown by increase time spent and number of
entries to the open arms of the maze (Table 3).
Interestingly, epi-inositol appeared to be even more
potent than myo-inositol in that model (data not
shown).
In contrast to the previous intraperitoneal findings,
an attempt to examine the consequences of oral
inositol treatment (5% in food for 2 weeks) in the
plus-maze did not indicate any anxiolytic-like effects
(Einat et al., unpublished observations). The observa-
tion that intraperitoneal but not oral inositol has
Table 3
Effects of chronic intraperitoneal inositol treatment on behavior in
the elevated plus-maze model of anxiety. Inositol significantly
increases ‘time spent in open arms’ and ‘number of entries to open
arms’
Behavior Inositol Control Significance level
Time spent in open 28.866.9 10.864.8 P 5 0.022
arms
Number of entries 2.560.6 1.160.4 P , 0.03
to open arms
118 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121
anxiolytic-like activity appears unusual because oral-
ly administered inositol was reported to increase
brain inositol levels and to have behavioral effects in
intact rats (Kofman et al., 1998). However, the fact
that SSRIs are effective in the treatment of patients
with anxiety disorders but do not have any anxiolytic
effects in normal controls (e.g. Gelfin et al., 1998)
suggested the hypothesis that inositol may be more
active in stressed than in unstressed animals. If that
is the case than rats chronically treated with in-
jections and therefore chronically stressed by that
paradigm, should respond more readily to inositol
treatment than rats who received inositol in their
food in a non-stressful manner. To test this hypoth-
esis two studies were designed that included: (a) an
examination of the effects of oral inositol treatment
after chronic mild stress; and (b) a study of the
effects of chronic oral inositol after acute stress
(Kofman et al., 2000).
1.3.2. Testing the relationship between stress levels
and the effects of inositol on anxiety-like behavior
The first study examined the effects of chronic
mild stress and inositol treatment in the elevated
plus-maze. Rats were divided to 4 groups (n 5 10 per
group) in a 2 3 2 design with oral inositol (5% in
food for 3 weeks) treatment as one factor and chronic
mild stress (daily saline injection 20 ml / kg for the
last 14 days of the experiment) as the second factor.
Results indicated that as shown before (e.g. Lister,
1987; Pellow et al., 1985; Treit et al., 1993), stress
had a significant effect on the performance of rats in
the elevated plus-maze. The effect of inositol on
behavior in the plus-maze was not significant but a
near-significant trend was demonstrated for the inter-
action between inositol and stress (data not shown).
This offers support to the hypothesis that inositol
effects on anxiety may be related to the level of
anxiety.
The second experiment was designed to test the
effects of chronic oral inositol treatment on anxiety-
like behavior after acute stress. The paradigm used to
induce stress was a single exposure to a cat. A single
exposure to a predator was demonstrated to increase
anxiety-like behaviors in rodents and was stipulated
to model pathologic anxiety mechanisms (Hendrei et
al., 1996) as well as behaviors related to PTSD
(Adamec and Shallow, 1993; Cohen et al., 1997b).
For the present experiment, rats were fed pellets
containing 5% inositol (n 5 10) or 5% 1:2 glucose
mannitol (n 5 10) for 19 days. On day 18 all rats
were exposed for 10 min to a domestic cat (no
physical contact was permitted) and 24 h later each
rat was tested in the elevated plus-maze. Results
indicate that inositol treatment reduced anxiety-like
behaviors in this paradigm as observed by a sig-
nificantly higher number of rats from the inositol
group that entered the open arms (8 / 10 in the
inositol group, 3 / 10 in the control group, x 2 5 5.05.
P , 0.02); by increased number of entries to the
open arms (t 5 2.48, P 5 0.024) and by a strong
trend of the inositol treated rats to spend more time
in the open arms than the control animals (t 5 2.0,
P 5 0.06).
The results of the last experiment combined with
the trend presented in the previous experiment add
support to the hypothesis that inositol’s anxiolytic-
like effect is stronger when the level of anxiety is
higher than normal.
1.4. Schizophrenia related studies
Amphetamine-induced hyperactivity and apomor-
phine-induced stereotypy are both frequently used to
models for some aspects of mania (Lyon, 1991a) and
schizophrenia (Lyon, 1991b) respectively. To evalu-
ate the possible effects of inositol in these models
two preliminary experiments were conducted (Kof-
man et al., 1993).
The first experiment was designed to evaluate the
effect of acute inositol treatment on amphetamine-
induced hyperactivity. Accordingly, 4 treatment
groups received treatment as follows: Group saline-
saline (n 5 8), Group saline-amphetamine (n 5 9),
Group glucose-amphetamine (n 5 8), and Group
inositol-amphetamine (n 5 9). Rats were injected
intraperitoneal with inositol or glucose (1 g / kg
diluted to 20 ml / kg) or an equivalent volume of
saline followed 2 h later by a SC injection of
amphetamine (0.75 mg / kg diluted to 1 ml / kg) or an
equal volume of saline. Five minutes after the SC
injection, rats were placed in activity monitors
(Optivarimax, Columbus Instruments, Columbus,
Ohio) and their activity automatically monitored for
20 min. Results indicate no observable effects of
inositol in this model (data not shown).
 H. Einat, R.H. Belmaker / Journal of Affective Disorders 62 (2001) 113 – 121
The second experiment tested the effects of acute
inositol treatment on apomorphine-induced
stereotypy. Rats received intraperitoneal pretreatment
with inositol (1 g / kg, 20 ml / kg), glucose (same dose
and dilution) or saline (same volume). Two hours
later they were injected SC with 0.5 mg / kg apomor-
phine and their level of stereotypy rated by two blind
observers according to a rating scale modified from
Kelly and Iverson (1976). Results did not reveal any
effects of inositol in this model (data not shown).
The last two experiments tested only acute inositol
treatment and that may diminish the possibility for
substantial conclusions regarding the effects of
inositol in these models. However, the effects of
classical anti-psychotic drugs in these models follow
acute treatment (for review see Lyon, 1991b) and
thus the results may be enough to conclude that
inositol is not acting in any similar way to these
drugs.
1.5. Memory related study ( Einat et al., 1998 b)
To test the effects of inositol on memory, 4
Rhesus monkeys were fed with 20 g / day inositol or
20 g 1:2 glucose:mannitol for 2 weeks in a cross
over design. Spatial discrimination tests (Olton et al.,
1980; Raveh et al., 1997) that permit the examina-
tion of a number of behavioral parameters with
emphasis on working and reference memory were
administered to the monkeys daily. Results indicate
no effects of inositol on any of the behavioral
parameters tested in this study (data not shown).
These results are consistent with the lack of effects
of inositol in Alzheimer’s patients (Barak et al.,
1996).
2. Discussion
The effects of inositol treatment on animal be-
havior were tested in different administration
schedules, doses and in a variety of situations
ranging from free behavior to designed animal
models of psychopathology. The collective results of
the studies described in the present paper indicate
that chronic inositol treatment may alleviate depre-
ssion-like and anxiety-like behaviors in rats. No
effects were observed in schizophrenia-related or
119
mania-related models and on memory-related tasks
in monkeys.
Clinical controlled trials of inositol in patients
with depression, panic disorder, OCD and PTSD
were small and positive psychoactive effects in
animals clearly strengthen the case for further clini-
cal trials and potential for general therapeutic use in
humans. A study of inositol in an animal model of
OCD would be a critical next step, although the
tentativeness of present animal models of OCD could
make this step an unsure one. The lack of inositol
effects on amphetamine-induced hyperactivity, an
animal model of mania, suggests that inositol may be
more anti-depressant than anti-bipolar. This is con-
sistent with its efficacy in panic disorder and OCD in
humans, where anti-bipolar drugs such as lithium are
ineffective. However, the effects of lithium on
inositol metabolism raise the speculation that inositol
might be lithium-like. This speculation is not sup-
ported by our rat model data.
The present data provide several animal behavioral
effects of inositol that are robust enough for pharma-
cological analysis. It will be important to determine
if inositol effects in the plus-maze and the swim test
are reversible with serotonin antagonists at specific
receptors, for instance. Such mechanistic data could
then stimulate hypotheses that would be testable in
patients under treatment with inositol, and perhaps
lead to etiological hypotheses related to the PI cycle.
Acknowledgements
The authors would like to thank Dr. Ora Kofman
and Dr. Hagit Cohen for their help. Supported by a
Stanley Foundation Center grant.
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