+

Class is Cancelled! Tuesday, Oct 16thMidterm #1 – Thursday, Oct. 4th

+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

+

Anatomy Basics

Major Division Ventricle Subdivision Principle Structures

Midbrain

Hindbrain

Forebrain

Lateral

Third

Telencephalon

Diencephalon

Cerebral cortex

Basal ganglia

Limbic System

Cerebralaqueduct Mesencephalon

Metencephalon

TectumTegmentum

Fourth

Cerebellum

Pons

Myelencephalon

Thalamus

Hypothalamus

Medulla oblongata

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Psychopharmacology

Chapter 4

Mind and Brain

+Chapter Preview

Principles of Psychopharmacology

Sites of Drug Action

Neurotransmitters and Neuromodulators

+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.

+Principles of Psychopharmacology

Pharmacokinetics The process by which drugs are absorbed, distributed

within the body, metabolized, and excreted.

+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

+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

+Principles of Psychopharmacology Routes of Administration

Intramuscular (IM) Injection – injection of a substance into a muscle.

+Principles of Psychopharmacology Routes of Administration

Subcutaneous (SC) Injection – injection of a substance into the space beneath the skin.

+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.

+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!

+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.

+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 lipid-soluble drugs.

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Depot Binding with Blood Albumin ProteinFigure 4.2

+Principles of Psychopharmacology

Inactivation and Excretion Enzymes deactivate drugs (e.g., liver). Drugs are eventually excreted (e.g., kidneys).

+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

+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

+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

+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.

+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.

+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

+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

+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

+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

+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

+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