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Class is Cancelled!
Tuesday, Oct 16th
Midterm #1 – Thursday, Oct. 4th
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Assignment

Due March 5th

Sign-up sheet for “lab component” located outside my office
(Sn 1061)

Sign-up for 1 hour slot – 4 people/time slot

Monday, Feb 11 - Friday, Feb 15
Major Division
Ventricle
Subdivision
Principle Structures
Cerebral cortex
Lateral
Telencephalon
Basal ganglia
Limbic System
Forebrain
Thalamus
Third
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Midbrain
Cerebral
aqueduct
Diencephalon
Mesencephalon
Anatomy Basics
Hypothalamus
Tectum
Tegmentum
Cerebellum
Hindbrain
Fourth
Metencephalon
Pons
Myelencephalon
Medulla oblongata
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Mind and
Brain
Psychopharmacology
Chapter 4
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Chapter Preview
 Principles
 Sites
of Psychopharmacology
of Drug Action
 Neurotransmitters
and Neuromodulators
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Introduction
 Psychopharmacology



The study of the effects of drugs on the nervous system and
behavior
Drug effects – the changes a drug produces in an animal’s
physiological processes and behavior
Sites of action – the locations at which molecules of drug
interact with molecules located on or in cells of the body,
thus affecting some biochemical processes of these cells.
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Principles of Psychopharmacology
 Pharmacokinetics

The process by which drugs are absorbed, distributed
within the body, metabolized, and excreted.
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Principles of Psychopharmacology
 Routes

of Administration
Intravenous (IV) Injection – injection of a substance
directly into a vein.
 Drug enters bloodstream immediately and reaches the
brain in seconds
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Principles of Psychopharmacology
 Routes

of Administration
Intraperitoneal (IP) Injection – injection of a substance
into the peritoneal cavity, the space that surrounds the
stomach, intestines, liver, and other abdominal organs.
 Most common route for small laboratory animals
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Principles of Psychopharmacology
 Routes

of Administration
Intramuscular (IM) Injection – injection of a substance
into a muscle.
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Principles of Psychopharmacology
 Routes

of Administration
Subcutaneous (SC) Injection – injection of a substance
into the space beneath the skin.
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Principles of Psychopharmacology
 Routes


of Administration
Oral Administration – administration of a substance into
the mouth so that it is swallowed.
Sublingual Administration – administration of a
substance by placing it beneath the tongue.
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Principles of Psychopharmacology
 Routes



of Administration
Intrarectal Administration – administration of a
substance into the rectum.
Inhalation – administration of a vaporous substance into
the lungs.
Topical Administration – administration of a substance
directly onto the skin or mucous membrane.
 Insufflation – sniffing drugs; contacts mucous
membranes of the nasal passages; sniffing not same as
inhalation!
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Principles of Psychopharmacology
 Routes


of Administration
Intracerebral Administration – administration of a
substance directly into the brain.
Intracerebroventricular (ICV) Administration –
administration of a substance into one of the cerebral
ventricles.
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Principles of Psychopharmacology

Distribution of Drugs Within the Body
 Lipid Solubility – ease with drug molecules are soluble
in fat.
 Heroin more lipid soluble than morphine so gets to
brain faster; more intense ”rush”
 Depot Binding – binding of a drug with various tissues
of the body or with proteins in the blood.
 If drug bound to depot cannot reach site of action
 Albumin – a protein found in the blood; serves to
transport free fatty acids and can bind with some lipidsoluble drugs.
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Depot Binding with
Blood Albumin
Protein
Figure 4.2
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Principles of Psychopharmacology

Inactivation and Excretion
 Enzymes deactivate drugs (e.g., liver).
 Drugs are eventually excreted (e.g., kidneys).
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Principles of Psychopharmacology
 Drug

Effectiveness
Dose-Response Curve – a graph of the magnitude of an
effect of a drug as a function of the amount of drug
administered.
+ Figure 4.3 A Dose-Response Curve
Usually defined as mg of drug/Kg of body weight
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Principles of Psychopharmacology
 Drug



Effectiveness
Sites of actions
Affinity – the readiness with which two molecules join
together
Many drugs have more than one effect, which should be
taken into consideration when determining the effect dose
for treatment.
+ Figure 4.4 Dose-Response Curves for
Morphine
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Principles of Psychopharmacology

Therapeutic Index – the ratio between the dose that
produces the desired effect in 50% of the animals and the
dose that produces toxic effects in 50% of the animals.
 If toxic dose is 5 times higher than the effective dose then
the TI = 5
 The lower the TI, the more care must be taken in
prescribing the drug
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Principles of Psychopharmacology
 Effects


of Repeated Administration
Tolerance – a decrease in the effectiveness of a drug that
is administered repeatedly.
 Withdrawal Symptom – the appearance of symptoms
opposite to those produced by a drug when the drug is
administered repeatedly and then suddenly no longer
taken.
Sensitization – an increase in the effectiveness of a drug
that is administered repeatedly.
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Principles of Psychopharmacology
 Placebo

Effects
An inert substance that is given to an organism in lieu of a
physiologically active drug; used experimentally to control
for the effects of mere administration of a drug.
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Sites of Drug Action
 Most
drugs that affect behavior affect synaptic
transmission
 Two


categories:
Antagonists – Drugs that oppose or inhibit the effects of a
particular neurotransmitter on the postsynaptic cell.
Agonists – Drugs that facilitate the effects of a particular
neurotransmitter on the postsynaptic cell.
+ Review of steps in synaptic
transmission (Chapter 2)

Neurotransmitters are synthesized and stored in synaptic vesicles

Vesicles travel to presynaptic membrane and dock

Axon fires and voltage-dependent calcium channels open allowing
calcium ions to enter

Calcium ions interact with docking proteins causing release of
neurotransmitter into synaptic cleft

Neurotransmitter binds to postsynaptic receptor, ion channels open, PSPs
produced

Effects of neurotransmitter kept brief by reuptake or enzymatic
degradation

Stimulation of autoreceptors regulates synthesis and release of
neurotransmitter
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Sites of Drug Action
 Act

on Neurotransmitters
Enzymes control the synthesis of a neurotransmitter from
its precursors.
 Rate of synthesis and release can be increased by
administering the precursor
 The precursor serves as an agonist (step 1 in Figure
4.5)
 If a drug inactivates the enzymes it prevents the
neurotransmitter from being produced
 It serves as an antagonist (step 2 in Figure 4.5)
+ Figure 4.5 Drug Affects on Synaptic
Transmission
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Sites of Drug Action
 Effects
on Storage and Release of
Neurotransmitters

Drugs may exert their agonistic or antagonistic effects by
influencing the storage and release of neurotransmitters.
 Some drugs can prevent the storage of neurotransmitter
in the vesicles – antagonists (step 3 in Figure 4.5)
 Some drugs can also prevent the release of
neurotransmitters by deactivating proteins that cause
synaptic vesicles to fuse with presynaptic membrane
(step 5 in Figure 4.5)
 Other drugs act as agonists by triggering the release of
neurotransmitter (step 4)
+ Figure 4.5 Drug Affects on Synaptic
Transmission
+
Sites of Drug Action
 Effects

on Receptors
Drugs may exert their agonistic or antagonistic effects by
influencing receptors.
 Direct Agonist – a drug that binds with and activates a
receptor; mimics the effects of a neurotransmitter (step 6
in Figure 4.5).
 Direct Antagonist – a drug that binds with a receptor
but does not activate it; prevents the natural ligand from
binding with the receptor; also called receptor blocker
(step 7 in Figure 4.5).
+ Figure 4.5 Drug Affects on Synaptic
Transmission
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Sites of Drug Action



Noncompetitive Binding – binding of a drug to a site on a
receptor; does not interfere with the binding site for the
principal ligand.
Indirect Antagonist – a drug that attaches to a binding site
on a receptor and interferes with the action of the receptor;
does not interfere with the binding site for the principal
ligand.
Indirect Agonist – a drug that attaches to a binding site on
a receptor and facilitates the action of the receptor; does
not interfere with the binding site for the principal ligand.
+ Figure 4.6 Drug Actions at Binding Sites
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Sites of Drug Action
 Autoreceptors
– regulate the amount of
neurotransmitter released


Drugs that activate these receptors serve as antagonists,
decreasing the amount of neurotransmitter released (step 8
in Figure 4.5)
Drugs that block the presynaptic autoreceptors increase
the release of neurotransmitter (step 9 in Figure 4.5)
+ Figure 4.5 Drug Affects on Synaptic
Transmission
+
Sites of Drug Action

Some terminal buttons form axoaxonic synpases

Presynaptic Heteroreceptor – a receptor located in the
membrane of a terminal button that receives input from
another terminal button by means of an axoaxonic synapse;
binds with the neurotransmitter released by the
presynaptic terminal button.
+ Figure 4.7 Presynaptic Heteroreceptors
+ Figure 4.8 Dendritic Autoreceptors
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Sites of Drug Action
 Effects
on Reuptake or Destruction of
Neurotransmitters



Drugs can attach to transporter molecules responsible for
reuptake and inactivate them
Drugs can bind with the enzyme that normally destroys the
neurotransmitter and prevent it from working
Both types of drugs prolong the presence the
neurotransmitter in the synaptic cleft – agonists (steps 10
and 11 in Figure 4.5).
+ Figure 4.5 Drug Affects on Synaptic
Transmission