PSYC 3030:

Neurochemical Basis
of Behaviour
University of Guelph
Dr. Sarah Thackray

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Announcements
• Exam 1: February 9, 2:30-3:50pm
• Covers from lecture 1 until end of Thursday’s (Feb 4)
lecture
• Out of 60 marks
• ~30 MC
• ~30 marks short answer: may include matching, labeling,
ordering, or short written answers
Last class…
• Chemical signaling between neurons
• Neurotransmitters
• Small molecule (“classical”), vs. neuropeptides vs.
lipid/gaseous transmitters
• Synthesis, release, inactivation
• Life cycle of vesicles
• Neurotransmitter receptors
• Ionotropic, metabotropic, tyrosine kinase (trk)
Lecture Objectives
• By the end of this lecture, you should be able to:
• Describe the different mechanisms through which drugs
can act
• Describe synaptic plasticity
• Describes the endocrine system and why it is important
to pharmacology
• Explain the criteria that need to be met for an animal
study to be useful
Pharmacology of Synaptic
Transmission
• Synaptic effects form the basis of almost all actions
of psychoactive drugs. They work by a variety of
mechanisms
Synaptic Plasticity
• Synaptic plasticity:
• Functional and structural synaptic changes including
change in strength, growth of new synapses, growth of
axon terminals, dendrites, spines, etc
• Synaptic change can result from
sensory/environmental stimuli, and from
psychoactive drugs—especially with repeated
exposure
Synaptic Plasticity
• A major player in synaptic plasticity is the mitogen-
activated protein kinase system (MAP kinase
system)
• MAP kinases respond to many different signaling
molecules
• Synaptic modulation by ERK, an element of the
MAP kinase system, has been implicated in the
mechanisms of memory formation
Synaptic Plasticity
• Neurons can rapidly change the size and shape of their
dendritic spines, grow new spines, and also lose some
• Most spines are formed during brain development
• Spines and synapses are “pruned” during adolescence,
but spines retain plasticity in the mature brain
• Spines may play an important role in formation of long-
term memories
• Many neurological disorders are associated with either
abnormally low or abnormally high numbers of
dendritic spines
Synaptic Plasticity
The Endocrine System
• Hormones are another form of cellular
communication
• Hormones are secreted by endocrine glands into
the bloodstream
Endocrine Glands
Adrenal Glands
• Adrenal glands: two glands that come together
during embryonic development
• Adrenal medulla: derived from nervous system
tissue; chromaffin cells secrete the monoamines
epinephrine (EPI) and
norepinephrine (NE)
• Stressors stimulate release of
EPI and NE as part of the
fight-or-flight response
Adrenal Glands
• Adrenal glands: two glands that come together
during embryonic development
• Adrenal cortex cells secrete glucocorticoids:
• Cortisol (hydrocortisone) in humans
• Corticosterone in rats and mice
Gonads
• Gonads (ovaries and testes) secrete:
• Estrogens (such as estradiol)
• Progestins (mainly progesterone)
• Androgens (such as testosterone)
• These hormones determine secondary sex
characteristics
Pituitary Gland
• Secretes many hormones, some control secretion of
hormones from other glands
• Anterior pituitary—connected to hypothalamus via
blood vessels
• Hypothalamic-releasing hormones made in the
hypothalamus travel to the anterior pituitary in the blood and
stimulate release of TSH, FSH, and LH, and ACTH
• Axons from neurons in the hypothalamus run through
the stalk and secrete hormones into blood vessels in
the posterior pituitary
• Vasopressin acts on the kidneys to increase water retention.
• Oxytocin stimulates uterine contractions during childbirth
and milk letdown during lactation
Other Glands
• Islets of Langerhans
• Cells secrete insulin and glucagon, which regulate glucose
levels; Both are peptide hormones
• Lack of insulin results in diabetes
• Thyroid gland
• Secretes thyroxine (T4) and triiodothyronine (T3), important
for normal energy metabolism
• Pineal gland
• Secretes melatonin, which is synthesized from the
neurotransmitter 5-HT
• Controls rhythmic functions. In humans, most secretion is at
night, suggesting control of sleep rhythms
Mechanism of Hormone Action
• Hormone receptors are on cell surfaces or are
intracellular
Why do we care about the
endocrine system?
• Drugs can alter hormone secretion and cause
physiological abnormalities
• Hormones can alter responses to drugs
• Hormones can have psychoactive properties (e.g.,
melatonin)
• Secretions from the pituitary are controlled by
neurotransmitter systems in the brain
• These systems can be altered by disease, injury, or drugs
Sex Hormones and Drug Abuse
• Researchers have found that sex hormones can
alter responses to drugs
• Levels of female sex hormones fluctuate with the
monthly menstrual cycle
Sex Hormones and Drug Abuse
• Researchers have found that sex hormones can
alter responses to drugs
• Levels of female sex hormones fluctuate with the
monthly menstrual cycle
• Good drug effect for smoked cocaine was greater in
females during the follicular phase, when levels of
progesterone are relatively low
• Similar results with nicotine
Summary
• Psychoactive drugs usually exert their effects by
modifying synaptic transmission
• Synaptic plasticity refers to functional and structural
changes in synaptic connectivity
• The MAP kinase system (including ERK) plays an important
role in the mechanisms of synaptic plasticity
• The endocrine system is important to pharmacology
studies for many reasons, including the fact that drugs
can affect hormone function, hormones may alter
behavioural responses to drugs, hormones themselves
may have psychoactive properties, and the endocrine
system can act as a window to the brain
Methods in
Psychopharmacology
Animal vs. Human Studies
• Animal studies permit superior control
• Living conditions regulated (i.e. diet, exercise,
temperature, etc.)
• History of animal subjects is well characterized
• Littermates, genetically altered animals available
• Animals more appropriate subjects for invasive
techniques
• E.g., examining toxicity
• Brain and behaviour or nonhuman mammals and
humans are similar enough for generalizations
Animal vs. Human Studies
• Results from controlled animal studies can validate
correlational relationships
• Example: Data collected on alcohol consumption during
pregnancy and occurrence of fetal alcohol syndrome
(FAS) suggest a relationship but do not show that alcohol
causes FAS

Correlation does not equal causation!

Bench to Bedside
• Translational research: transforming discoveries
from basic neuroscience research into clinical
applications
Behavioural Pharmacology
• Neurobiological techniques tell us very little unless
we have an objective measure of the behavioural
consequences
• Behavioural measures help to…
• Evaluate the effects of drugs on behaviour
• Develop animal behaviour models of psychiatric
disorders
• Preclinically screen the large number of newly
synthesized drugs
• Testing is done in a controlled and systematic way
Evaluating Animal Behaviour
• Ideally, animal tests should have:
• High face validity
• Tests closely resemble those used on humans (e.g.,
blood pressure)
• To compare symptoms normally described in human
terms, such as guilt, delusions, altered mood. etc., a
quantifiable measure of animal behavior is substituted
(low face validity)
• Predictive validity
• The drug effects observed in laboratory tests closely
parallel or predict the clinical effect
Evaluating Animal Behaviour
• Ideally, animal tests should have:
• Construct validity
• The extent to which the animal measurement tool
actually measures the characteristic being investigated
• Have high reliability
• The same results will be recorded each time the test is
used
• The same rank order of potency in the animal test
as the order of potency of the therapeutic action of
the drugs
Summary
• Advantages of animal testing include having a
subject population with similar genetic background
and history, maintaining highly controlled
environments, and being able to use invasive
neurobiological techniques
• Techniques in behavioural pharmacology provide a
means for quantifying animal behaviour for drug
testing, developing models of psychiatric disorders,
and evaluating the neurochemical basis of
behaviour