Chapter Four Psychopharmacology

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Psychopharmacology

Chapter Four

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• Neurotransmitters – Participate in directed synapses by acting on

neurons in their own immediate vicinity

• Neuromodulators and neurohormones– Participate in nondirected synapses by acting

on more distant neurons– Neuromodulators communicate with target

diffuse away from the point of release– Neurohormones travel in the blood supply to

reach their final targets

Neurotransmitters, Neuromodulators, and Neurohormones

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Neuromodulators and Neurohormones

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• Substances released by one cell that produce a reaction in a target cell

• The substance: – Must be present within a presynaptic cell.– Is released in response to presynaptic

depolarization– Interacts with specific receptors on a

postsynaptic cell

Identifying Neurochemicals

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Types of Neurochemicals

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Features of Small-Molecules and Neuropeptides

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• Produced in cholinergic neurons • Two receptor types:

– Nicotinic receptors– Muscarinic receptors

Small-Molecule Neurochemicals: Acetylcholine

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The Distribution of Cholinergic Systems in the Brain

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• Catecholamines– Dopamine, norepinephrine, epinephrine– Synthesized from tyrosine

• Indoleamines– Serotonin, melatonin– Serotonin is synthesized from tryptophan

Small-Molecule Neurochemicals: Monoamines

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Catecholamines Share a CommonSynthesis Pathway

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• Dopaminergic neurons in the midbrain form connections with other neurons

• Dopamine activity is associated with motivated behavior and reward processing

Dopaminergic Systems in the Brain

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Dopaminergic Systems in the Brain (cont’d.)

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• Norepinephrine– Noradrenergic neurons– Increases arousal and vigilance– Primary neurotransmitter in the sympathetic

nervous system

• Epinephrine– Adrenergic neurons– Regulation of eating, blood pressure

Noradrenergic Systems in the Brain

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Noradrenergic Systems in the Brain (cont’d.)

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• Synthesized from tryptophan• Regulates mood, sleep, and appetite

Indoleamines: Serotonin

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Serotonergic Pathways in the Brain

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• Synthesized from histidine• Associated with wakefulness

Histamine

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• Major excitatory neurotransmitter in the CNS

• Subtypes of glutamate receptors: NMDA, AMPA, and kainate

Amino Acid Messengers: Glutamate

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• Major inhibitory neurochemical in the CNS• Synthesized from glutamate• GABAA and GABAB receptors

– GABAA receptors interact with psychoactive drugs

Amino Acid Messengers: GABA

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The GABAA Receptor Interacts with Several Drugs

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• Major inhibitory neurochemical in spinal cord interneurons

• Excitatory function with glutamate at NMDA receptors

• Synthesized from serine

Amino Acid Messengers: Glycine

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• Act in the CNS and in connections between autonomic neurons and the vas deferens, bladder, heart, and gut– ATP is associated with pain perception and

sleep-waking cycles– Adenosine inhibits the release of many

neurochemicals

ATP and Adenosine

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• Substance P (pain perception)• Endorphins act on same receptors as

opioids and heroin• Insulin and cholecystokinin function in

digestion and as neuromodulators and neurohormones

• Oxytocin and vasopressin act as neuromodulators and neurohormones

Neuropeptides

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Distribution of Endorphin Receptors in the Human Brain

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• Diffuse through membranes and interact with intracellular receptors

• Transmits information from the postsynaptic to the presynaptic neurons

• Nitric oxide (NO)– Neural communication, maintenance of blood

pressure, erection (target of Viagra)

Gasotransmitters

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• Agonists enhance the activity of a neurotransmitter

• Antagonists reduce the activity of a neurotransmitter

Drug Actions at the Synapse

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• Neurochemical production– Manipulating the synthesis of a

neurotransmitter may affect the amount available for release

• Neurochemical storage– Interfering with the storage of a

neurotransmitters in vesicles within a neuron

• Neurochemical release– Can be modified in response to the arrival of

an action potential by drugs

Mechanisms of Drug Actions at the Synapse

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• Mimic the action of a neurotransmitter at the site

• Block the synaptic activity by occupying a binding site

• Influence the activity of the receptor

Mechanisms of Drug Actions at the Synapse: Receptor Effects

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Drug Interactions at the Cholinergic Synapse

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Drug Interactions at the Dopaminergic Synapse

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Drug Interactions at the Serotonergic Synapse

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• Reuptake effects– Cocaine, amphetamine, and Ritalin inhibit

dopamine reuptake– SSRIs (e.g., Prozac) inhibit serotonin

reuptake

• Enzymatic degradation– Organophosphates interfere with AChE

• Deactivation of neurotransmitters

Reuptake Effects and Enzymatic Degradation

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• Administration of drugs– Method of administration leads to different

effects on nervous system; blood-brain barrier

• Individual differences– Drug effects influenced by body weight,

gender, and genetics

• Placebo effects– User expectations influence drug effects– Double-blind experiment

Basic Principles of Drug Effects

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Concentration of a Drug in the Blood Supply Depends on the Method of Administration

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• Tolerance – Lessened effects as a result of repeated

administration

• Withdrawal– Occurs when substance use is discontinued;

opposite of the effects caused by the discontinued drug

• Addiction– Compulsive need to use the drug repeatedly

despite harm to the user

Tolerance, Withdrawal, and Addiction

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Vaccinations Against Drugs of Abuse

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• Increase alertness and mobility– Caffeine – adenosine antagonist– Nicotine – nicotinic cholinergic receptor

agonist – Cocaine – dopamine reuptake inhibitor– Amphetamine – stimulates release and

inhibits reuptake of dopamine/norepinephrine– Ecstasy (MDMA) – stimulates release of

serotonin and oxytocin; toxic to serotonergic neurons

Effects of Psychoactive Drugs: Stimulants

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Caffeine Content of Common Products

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Caffeine Content of Common Products (cont’d.)

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Health Consequences of Methamphetamine Abuse

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Historical Use of Cocaine

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Ecstasy Damages Serotonergic Neurons

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• Interact with endorphin receptors– Pain relief, relaxation, sense of euphoria

• Opiates– Derived from sap of opium poppy– Morphine, codeine – Heroin

• Synthetic opiate• Derived from morphine

Opioids

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• Active ingredient THC is an endogenous cannabinoid receptor agonist

• Cannabinoid receptors are in the hippocampus and prefrontal cortex

• Effects: mild euphoria, perceptual distortion, hallucination, and depression

Marijuana (Cannabis)

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Cannabis and the Risk of Psychosis

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• Serotonergic agonist• No known medicinal value• Hallucinogens• Use results in tolerance, but not addiction

or withdrawal• Flashbacks with extended use

LSD

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• GABAA receptor agonist • Stimulates dopaminergic reward pathways• Rapid tolerance• Damaging effects on health

Alcohol

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Alcohol and Mortality