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Psychopharmacology

Chapter Four

• 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

Neuromodulators and Neurohormones

• 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

Types of Neurochemicals

Features of Small-Molecules and Neuropeptides

• Produced in cholinergic neurons • Two receptor types:

– Nicotinic receptors – Muscarinic receptors

Small-Molecule Neurochemicals: Acetylcholine

The Distribution of Cholinergic Systems in the Brain

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

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

Small-Molecule Neurochemicals: Monoamines

Catecholamines Share a Common Synthesis Pathway

• 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

Dopaminergic Systems in the Brain (cont’d.)

• 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

Noradrenergic Systems in the Brain (cont’d.)

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

Indoleamines: Serotonin

Serotonergic Pathways in the Brain

• Synthesized from histidine • Associated with wakefulness

Histamine

• Major excitatory neurotransmitter in the CNS

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

Amino Acid Messengers: Glutamate

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

– GABAA receptors interact with psychoactive drugs

Amino Acid Messengers: GABA

The GABAA Receptor Interacts with Several Drugs

• Major inhibitory neurochemical in spinal cord interneurons

• Excitatory function with glutamate at NMDA receptors

• Synthesized from serine

Amino Acid Messengers: Glycine

• 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

• 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

Distribution of Endorphin Receptors in the Human Brain

• 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

• Agonists enhance the activity of a neurotransmitter

• Antagonists reduce the activity of a neurotransmitter

Drug Actions at the Synapse

• 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

• 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

Drug Interactions at the Cholinergic Synapse

Drug Interactions at the Dopaminergic Synapse

Drug Interactions at the Serotonergic Synapse

• 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

• 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

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

• 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

Vaccinations Against Drugs of Abuse

• 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

Caffeine Content of Common Products

Caffeine Content of Common Products (cont’d.)

Health Consequences of Methamphetamine Abuse

Historical Use of Cocaine

Ecstasy Damages Serotonergic Neurons

• 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

• 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)

Cannabis and the Risk of Psychosis

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

or withdrawal • Flashbacks with extended use

LSD

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

Alcohol

Alcohol and Mortality