Chapter 4: Psychopharmacology

Overview of Lecture

Psychopharmacology Issues

Synaptic Transmission

Acetylcholine (ACh)

Serotonin (5-HT)

Psychopharmacology

Drugs exert effects on nervous system to alter behavior

Assumptions about drugs:

Viewed as "exogenous" chemicals

Alter neuron activity

Have effects at low doses

Pharmacokinetics

Drug molecules must reach target sites

Pharmacokinetics: study of drug absorption, distribution within body, and elimination

Routes of drug administration into the body

Intravenous (IV): into a vein

Intraperitoneal (IP): into the gut (lab animals)

Subcutaneous (SC): under the skin

Intramuscular (IM): into a muscle

Drug Effectiveness

Dose-response (DR) curve: Depicts the relation between drug dose and magnitude of drug effect

Different drugs have different D-R curves

Different sites of action

Different levels of affinity

Drug Effects Vary with
Repeated Administration

Overview of Synaptic Transmission

Transmitter substances are

Synthesized, stored, released, and terminated

Susceptible to drug manipulation

Definitions:

Agonist: binds to and activates receptors

Antagonist: binds to but does not activate receptors

Direct effects: at the postsynaptic receptor

Inverse agonist: binds to alternative site, prevents ion channel from opening

Definitions

Neurotransmitter

Synthesized and released from presynaptic terminal

Has brief effects on postsynaptic membrane

Glutamate (excitatory) and GABA (inhibitory)

Neuromodulator

Modulates ongoing activity rather than transmitting information

ACh: Localization

In periphery: ACh neurons are found in:

Autonomic ganglia (e.g. the heart)

Neuromuscular junction

In brain: ACh neurons are found in:

Dorsal pons

Septum

Basal forebrain

ACh Synthesis

Synthesis pathway:

Acetyl CoA+Choline --ACh

CoA arises from glucose metabolism

Dependent on choline

Blocked by NVP

ACh Release

CA⁺⁺ is required for ACh release

ACh release is blocked by Vesamicol (prevents ACh transport into vesicles)

Increased choline supply can increase ACh release

ACh release is promoted by black widow venom, bungarotoxin

ACh release is blocked by botulinum toxin

ACh Receptors

Nictotinic: found in skeletal muscle (ionotropic effect)

Agonists: ACh, nicotine

Antagonists: d-tubocurarine and curare

Muscarinic: found in heart and smooth muscle (metabotropic)

Agonists: ACh, muscarine

Antagonists: atropine and scopolamine

ACh: Termination of Transmitter Effect

ACh: Some Behavioral Actions

Neuromuscular junction is cholinergic

Cholinergically-induced thirst

Cholinergic component of Alzheimer’s

Reduced cortical ACh in Alzheimer’s patients

Damage to ACh cells in nuc. basalis Meynert

ACh antagonists impair memory

Nicotine stimulates thermogenesis which reduces body weight (e.g. 10 lb. weight gain in ex-smokers)

5-HT:Localization

5-HT found in

Gut (98%)

Brain (2%)

Pineal

PVN

Raphe nuclei

5-HT Synthesis

5-HT: Release and Termination

Release:

8-OHDPAT is auto agonist => 5-HT release

No selective release blocker for 5-HT

Fenfluramine is releasing agent

Termination:

Reuptake is blocked by fluoxetine (elevates 5HT)

Degradation: MAO converts to 5-HIAA

Iproniazid blocks MAO

5-HT Receptors

Nine types of 5-HT receptors

5-HT₁: 1A, 1B, 1D, 1E, and 1F

5-HT₂ : 2A, 2B, and 2C

5-HT₃

5-HT₁ and 5-HT₂ receptors are metabotropic

5-HT₃ receptors are ionotropic

5-HT: Behavioral Actions

Food intake:

Increased by 8-OHDPAT

Decreased by fenfluramine (5HT_1aagonist)

Pain sensitivity (reduced 5-HT = increased pain sensitivity)

Slow-wave sleep and 5-HT

5-HIAA levels are low in suicide victims

5HT_1b agonists: decrease aggression

5HT_1aagonists: increase male sexual behavior