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Chapter Four Psychopharmacology Version Dated 21 Sep 2009 CHAPTER 4 PSYCHOPHARMACOLOGY Neurotransmitters, Neuromodulators, and Neurohormones • Identifying Neurotransmitters – Must be synthesized within the neuron – In response to an action potential, the substance is released in sufficient quantities to produce an effect in the postsynaptic cell – We should be able to duplicate the action of a suspected neurotransmitter experimentally on a postsynaptic cell – Some mechanism exists that ends the interaction between the neurotransmitter and the postsynaptic cell Figure 4.2 Major Categories of Neurotransmitters, Neuromodulators, and Neurohormones Neurotransmitters • Types of Neurotransmitters – Small molecule transmitters – meet all or most of criteria and play a vital role in neurotransmission – Neuropeptides – at least 40 act as neurotransmitters, neuromodulators, and neurohormones – Gaseous neurotransmitters – some gases transfer information from one cell to another Table 4.1 Features of Small-Molecule Transmitters and Neuropeptides Figure 4.3 The Distribution of Cholinergic Systems in the Brain Figure 4.4 Catecholamines Share a Common Synthesis Pathway Figure 4.5 Dopaminergic Systems in the Brain Figure 4.6 Noradrenergic Systems in the Brain Figure 4.8 The Distribution of Serotonergic Pathways in the Brain Figure 4.9 The NMDA Glutamate Receptor Figure 4.10 The GABAA Receptor Interacts with Several Drugs Figure 4.11 Distribution of Opiate Receptors in the Human Brain Drug Actions at the Synapse • Agonists enhance the activity of a neurotransmitter • Antagonists reduce the activity of a neurotransmitter Drug Actions at the Synapse • Neurotransmitter Production – Manipulating the synthesis of a neurotransmitter will affect the amount available for release • Neurotransmitter Storage – Interfering with the storage of a neurotransmitters in vesicles within a neuron • Neurotransmitter Release – Drugs can modify the release of a neurotransmitter in response to the arrival of an action potential Drug Actions at the Synapse • Receptor Effects – Can mimic the action of a neurotransmitter at the site – Can block the synaptic activity by occupying a binding site – Can influence the activity of the receptor • Reuptake Effects and Enzymatic Degradation – Deactivation of neurotransmitters Figure 4.12 Drug Interactions at the Cholinergic Synapse Figure 4.14 Drug Interactions at the Dopaminergic Synapse Figure 4.15 Drug Interactions at the Serotonergic Synapse Basic Principles of Drug Effects • 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 Figure 4.16 Concentration of a Drug in the Blood Supply Depends on the Method of Administration Basic Principles of Drug Effects • Tolerance and Withdrawal – 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 – Causes of addiction – Treatment of addiction Figure 4.17 Tolerance and Withdrawal Can Result from Compensation Figure 4.18 The Nucleus Accumbens Participates in Reward and Addiction Effects of Psychoactive Drugs • Stimulants – increase alertness and mobility – Caffeine – antagonist for adenosine – Nicotine – agonist at the nicotinic cholinergic receptor – Cocaine and Amphetamine • Cocaine – dopamine reuptake inhibitor • Amphetamine – stimulates dopamine and norepinephrine release and inhibits their reuptake – Club Drugs: Ecstasy and GHB • MDMA – stimulates release of serotonin and oxytocin; toxic to serotonergic neurons • GHB – mimics inhibitory effects of GABA MDMA Ecstasy Destroys Serotonergic Neurons Figure 4.20 Caffeine Content of Common Products Effects of Psychoactive Drugs • Opiates – Synthesized from sap of opium poppy – Morphine, codeine, heroin – Endorphin receptors • Marijuana – THC – agonist at receptors for endogenous cannabinoids – Cannabinoid receptors in the hippocampus and prefrontal cortex Effects of Psychoactive Drugs • Other hallucinogens – have the ability to produce false perceptions – Mushrooms – agonist for GABA and glutamate – Mescaline – acts on serotonergic neurons – Phencyclidine (PCP) – antagonist at the NMDA glutamate receptor – LSD – serotonergic agonist Effects of Psychoactive Drugs • Alcohol – Agonist at the GABAA receptor – Stimulates dopaminergic reward pathways – Damaging effects on health • St. John’s Wort – Effective for mild depression – Interactions with other drugs