PSYC 460 - Neurotransmitters (These are my lecture notes on neurotransmitters. I may not have mentioned all of this in class this time. Use you own class notes as a guide.) I. the discovery of neurotransmission - Otto Loewi and the frog heart A. muscle fibers are a lot like axons - they contract by generating "action potentials" due to ion fluxes B. heart muscle fibers are spontaneously excitable - no input is needed from the NS to keep the heart beating (the heartbeat is myogenic) 1. however, innervation from the ANS can speed up or slow down the heartbeat a. stimulation of the vagus nerve slows down the heart b. this happens even if the heart-nerve preparation is isolated from the body 2. if fluid from the bath of one such preparation is removed and added to the bath of a second preparation... a. the second heart also begins to beat more slowly, provided... i. the vagus nerve had been stimulated in the first prep. ii. the fluid was transferred immediately after this stimulation b. Loewi concluded that this could only be because some chemical, released from the vagus nerve into the first bath, was being transferred to the second bath i. he called the chemical vagusstoff ("stuff from the vagus nerve") ii. von Euler, a Swedish chemist, eventually identified it as acetylcholine II. acetylcholine A. location 1. neuromuscular junction - excitatory on muscle fibers (nicotinic) 2. ANS - e.g., PSNS innervation of the heart (inhibitory) 3. brain (mostly muscarinic) a. learning and memory b. REM sleep c. general activation of cortex - emotion, motivation, etc. B. biosynthesis - from dietary choline and acetate (acetic acid) C. inactivation - by acetylcholinesterase in the synaptic cleft (choline is then recycled by reuptake) D. receptors - two types 1. nicotinic (ionotropic) - muscle fibers and some in spinal cord 2. muscarinic (metabotropic) - CNS and target organs of PNS E. pharmacology 1. nicotine - an agonist at nicotinic receptors 2. curare - an antagonist at nicotinic receptors (paralytic, arrow poison) 3. alpha-bungarotoxin (from the venom of the banded krait) - an irreversible antagonist! 4. botulinum toxin - blocks release 5. black widow spider venom - stimulates release 6. many insecticides - irreversible AChE inhibitors 7. physostigmine, neostigmine - reversible AChE inhibitor 8. belladonna alkaloids (deadly nightshade) - atropine and scopolamine (antagonists at muscarinic receptors) III. GABA (gamma-aminobutyric acid) A. neurotransmitter at the vast majority of inhibitory synapses in the CNS, especially in the brain - located throughout the brain, mostly in neurons making local circuits B. biosynthesis - from glutamate (glutamic acid, an amino acid) C. inactivation - enzymatically by GABA transaminase into glutamate which is then recycled by reuptake D. receptors - 2 subtypes (at least) 1. GABA-B receptor - not well understood 2. GABA-A receptor a. ionotropic gating a chloride channel b. allosteric sites - for benzodiazepines, etc. E. pharmacology 1. benzodiazepines and barbiturates 2. convulsants a. bicuculine, picrotoxin - antagonists b. Metrazol - blocks release (once used to induce convulsion in therapy) 3. date rape drugs a. "roofies" (Rohypnol) - a benzodiazepine b. GHB - gamma-hydroxybutyrate IV. amino acids (not including GABA) A. glycine - inhibitory in the spinal cord and lower brainstem 1. nonessential amino acid 2. pharmacology - fortunately, there are few drugs that influence glycine a. tetanus toxin - blocks release b. strychnine ('neen') - from the tree Strychnos nux vomica, causes convulsion that are brought on by any sensory stimulus (also used as a rat poison) B. glutamate (glutamic acid) - appears to be the principle excitatory neurotransmitter throughout the brain 1. nonessential amino acid 2. receptors - at least 5 types, including the NMDA receptor V. catecholamines - one of the two classes of monoamine neurotransmitters A. biosynthesis - tyrosine (a nonessential amino acid) to l-dopa to dopamine to norepinephrine to epinephrine B. location - call bodies are in the PNS (NE), locus coeruleus (NE), substantia nigra (DA), and ventral tegmental area(DA) 1. ANS - emotional arousal (NE) 2. reticular formation - arousal, vigilance (NE) 3. limbic system - emotion (NE and DA) 4. basal ganglia - voluntary movement (DA) a. lost in Parkinson's disease due to degeneration in the substantia nigra b. precursor loading therapy - l-dopa, but not DA or tyrosine i. DA does not cross blood-brain barrier ii. the TyrOHase enzyme is already saturated with precursor and is subject to end-product inhibition C. inactivation 1. primarily by reuptake 2. but also enzymatically - MAO, others(?) D. receptors - many, many different types 1. alpha and beta for NE 2. D1 - D5 for DA E. pharmacology - will be discussed in detail under PSYCHOPHARMACOLOGY (amphetamine, cocaine, antidepressants, etc.) VI. indoleamines - the other class of monoamines A. biosynthesis - from tryptophan (an essential amino acid) B. location - cell bodies are in the raphe nuclei 1. limbic system - mood 2. reticular formation - sleep 3. sensory cortex 4. pain areas in lower brainstem C. inactivation 1. by reuptake 2. MAO D. receptors - many, many types and subtypes E. pharmacology - will be discussed in detail under PSYCHOPHARMACOLOGY (antidepressants - SSRIs, hallucinogens) VII. lipid-derived A. anandamide - the natural ligand for THC receptors B. 2-AG - may be another natural ligand for THC receptors VIII. peptides A. protein precursors are biosynthesized in cell body and sent to terminals via orthograde axoplasmic transport - along the way, peptides are snipped out of the protein B. endorphins 1. location - CNS, esp. limbic system where they regulate pain sensitivity and mood 2. pharmacology - opioids C. vasopressin and oxytocin IX. neuromodulation (This is a plain text document. Hit your browser's Back button to return to the PSYC 460 main page.)