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PSYB64H3 (201)
Chapter 4

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Janelle Leboutillier

4 | Psychopharmacology Neurotransmitters, Neuromodulators, Neurohormones - neurotransmitters: chemical messenger that communicates across a synapse - neuromodulators: chemical messenger that communicates w/ target cells more distant than synapse by diffusing away from point of release - neurohoromone: chemical messenger that communicates w/ target cells at great distance, often by traveling through circulation Identifying Neurotransmitters - agree w/ additional criteria: 1) neurotransmitter must be synthesized w/in neuron 2) in response to arrival of action potential = substance released in sufficient quantities = produce effect on postsynaptic cell 3) should be able to duplicate action of suspected neurotransmitter experimentally on postsynaptic cell 4) a mechanism exists that ends interaction between neurotransmitter and postsynaptic cell Types of Neurotransmitters - figure 4.2, p.96 – major categories of neurotransmitters, neuromodulators, and neurohormones - table 4.1, p.97 – features of Small-Molecule Transmitters and Neuropeptides The Small-Molecule Transmitters - meet most or all of preceding criteria specific for neurotransmitters and appear to play vital role in neurotransmission:  acetylcholine  5 monoamines  amino acids  energy molecule adenosine triphosphate (ATP) - acetylcholine (ACh): used at neuromuscular junction, in autonomic nervous system and central nervous system  neurons that use this as major neurotransmitter are referred as cholinergic neurons  cholinergic neurons  use building blocks o choline – obtained from dietary fats o acetyle coenzyme A (acetyl CoA) – results from metabolic activites of mitochondria  enzyme choline acetyltransferase (ChAT) o acts on two building blocks (or precursors) = produce acetylcholine o useful marker for identifying cholinergic neurons o only found in neurons that produce ACh  also produces acetylcholinesterase (AChE): enzyme that breaks down acetylcholine o choline from breakdown = recaptured by presynaptic neuron and resynthesized into more ACh - ACh is primary neurotransmitter at neuromuscular junction = synapse between neuron and muscle fiber  essential to operation of autonomic nervous system  all preganglionic synapses use ACh as neurotransmitter  same w/ postganglionic synapses in parasympathetic division - cholinergic neurons important in peripheral nervous system, widely distributed in brain  figure 4.3, p.97  major groups of cholinergic neurons located in: basal forebrain, septum, and brainstem – project to neocortex (sight and hearing in mammals), hippocampus, and amygdala  these areas especially likely to deteriorate because of Alzheimer’s  given memory loss associated w/ this disease, neurons appear to participate in learning and memory - many subtypes of cholinergic receptors found  two major subtypes 1) nicotinic receptors: postsynaptic receptor that responds to nicotine and ACh 2) muscarinic receptors: postsynaptic receptor that responds to both ACh and muscarine o derived from hallucinogenic – mushroom amanita muscaria - difference between nicotinic and muscarinic receptors  mechanism of action  N = ionotropic receptors  M = metabotropic  location  N = neuromuscular junction (speed for muscular responses)  CNS and ANS contain both (M more common in CNS - five monamines: one of major group of biogenic amine neurotransmitters  further divided into two subgroups 1) catecholamines (dopamine, norepinephrine, and epinephrine) 2) indoleamines (serotonin and melatonin)  all monamines subject to reuptake from synaptic gap following release  monamines not enased in vesicle w/in axon terminal  nroken down by enzyme monoamine oxidase (MAO) - figure 4.4, p.98 – catecholamines share common synthesis pathway  begins w/ amino acid tyrosine  neurons also contain enzyme tyrosine hydroxylase (TH)  when TH acts on tyrosine = L-dopa  production of dopamine  enzyme dopa decarboxylase acts on L-dopa  dopamine converted to norepinephrine  action of enzyme dopamine -hydroxylase (DBH)  takes place w/in vesicles  epinephrine  reaction between norepinephrine and enzyme phenylethanolamine N- methyltransferase (PNMT)  PNMT located in intracellular fluid of axon terminal of neurons that use epinephrine  Once norepinephrine synthesized in synaptic vesicles = released into intracellular fluid = interact w/ [NMT = epinephrine  Epinephrine transported into vesicles - dopamine widely distributed throughout brain – involved w/ systems mediating movement, reinforcement, and planning  figure 4.5, p.99 – dopaminergic systems in the brain  projections from substantia nigra (midbrain) to basal ganglia (cerebral hemispheres)  mesolimbic system – ventral tegmentum (midbrain), projects to parts of limbic system = hippocampus, amygdala, and nucleus accumbens o mesolimbic: feelings of reward, play important role in addiction  ventral gementum, projects to parts of frontal lobe o higher-lvl cognitive functions (e.g., planning of behaviour)  subtypes of receptors – D -1 (i5 order of discovery  all metabotropic  D (and probably D and D ) – serve as postsynaptic receptors and presynaptic autoreceptors 2 3 4 (help presynaptic neuron monitor synthesis and release of neurotransmitter substance o D im2licated in both reward and psychotic behaviour - neurons releasing epinephrine = adrenergic; neurons releasing norepinephrine = noradrenergic - epinephrine plays limited role as CNS neurotransmitter  “adrenalin rush”  result from release of epinephrine from adrenal glands located above kidneys in lower back into blood supply  figure 4.6, p.100 – noradrenergic systems in the Brain  neurons secreting norepinephrine – pons, medulla, and hypothalamus  most significant  locus coeruleus of pons  project to spinal cord and nearly every major part of brain o major primary result of activity = increase arousal and vigilance o in PNS  found at postganglionic synapse of sympathetic nervous system, involved in arousal  at least four receptor sites respond to norepinephrine or epinephrine  found in both CNS and organs that respond to sympathetic nervous system activity and neurohormones  all metabotropic - indoleamines  serotonin: believed to participate in regulation of mood, sleep, and appetite  figure 4.7, p.100 – synthesis of serotonin  amino acid tryptophan – obtained from dietary sources (grain, meat, and dairy)  two chemical reactions = convert tryptophan into serotonin 1) action of enzyme tryptophan hydroxylase = converts tryptophan to 5-hydroxytryptophan (5-HTP) 2) 5-HTP converted to serotonin  action of enzyme 5-HTP decarboxylase  figure 4.8, p.101 – distribution of serotenergic pathways in the brain  few in #, as few as 200 000 in the human brain  most located in raphe nuclei (brainstem) – projects travel to spinal cord, cerebellum, limbic system, and neocortex  implicated in behaviours like sleep, mood, and appetite  at least 15 subtypes of receptors – most function as metabotropic - amino acid neurotransmitters  two most significant: 1) glutamate: major excitatory; 2) gamma-aminobutyric acid (GABA):major inhibitory  glutamate (aka glutamic acid) = among 20 basic amino acids used to build other proteins o not GABA  glutamate most frequently used excitatory neurotransmitter in CNS  synthesized from -ketoglutarate o once released  taken up by neurons and astrocytes o synaptic area must be cleared of excess glutamate – extended action could be toxic o some oversensitive to monosodium glutamate (MSG) – adverse reactions include chest pain, headache, nausea, and rapid heartbeat  FDA views it as safe for most adults  Glutamate has receptors either ionotropic or metabotropic  three major ionotropic named after external substances that activate them (same as ACh) 1) N-methyl-D-aspartate (NMDA) 2) Alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid
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