181lec9.key - Psych 181: Dr. Anagnostaras Lec 9: Nicotine 1...

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Psych 181: Dr. Anagnostaras Lec 9: Nicotine Nicotine Alkaloid in tobacco 5% by weight Tobacco smoke is a very complex mixture carbon monoxide thousands of particulates nicotine major psychoactive agent cigarette: ~9 mg; 1 mg absorbed N CH3 N Nicotine Routes Inhalation (smoking) via lungs (25% reaches brain within 7-sec) Oral (chewing, moist snuff, gum) via oral membranes Nasal (snuff) via membranes of nasal cavities N CH3 N Nicotine 1 2 3 Sunday, January 9, 2011
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History of use Absorption Time (min) –10 30 60 90 120 4 8 20 16 12 Cigarettes Oral snuff Chewing tobacco Nicotine gum Blood nicotine (ng/ml) Most routes very effective • rapid repeated administration unique to cigarettes • one pack per day= 7,300 cigarettes per year 14.1 4 5 6 Sunday, January 9, 2011
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Metabolism and excretion Kidney and liver Short half-life (~ 2 hr) Milk Peripheral effects Sympathetic increase heart rate increase blood pressure secretion of NE and E from adrenals vasoconstriction Parasympathetic increase stomach acid increase intestinal motility Toxicity (60 mg, or half a cigar)-pesticides CNS effects Psychomotor performance Reinforcement Unit dose (mg/kg) Active Inactive 0.003 0 0.01 0.03 0.06 20 60 80 100 0.1 0.3 0.5 Number responses Intake (mg/kg) 14.2 7 8 9 Sunday, January 9, 2011
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Mechanism of action Nicotinic acetylcholine receptor Acetylcholine First transmitter identifed peripheral nervous system Acetylcholine H 3 C N + CH 2 CH 2 CH 3 O C CH 3 O CH 3 Synthesis Choline Acetyl coenzyme A Choline acetyltransferase Choline + AcCoA ChAT ACh + HSCoA AcCoA 7.1 10 11 12 Sunday, January 9, 2011
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Receptors and metabolism Agonists muscarine nicotine Antag. atropine α -bungar- toxin curare Choline transporter ACh Choline + acetate Na+ Na+ ACh ACh AChE Choline Muscarinic receptor Nicotinic postsynaptic receptor Acetylcholinesterase Distribution 7.8 Nucleus accumbens Medial septal and diagonal band nuclei Nucleus basalis and substantia innominata Olfactory bulb Caudate– putamen Thalamus Hippocampus Pons Pontine reticular nuclei Olfactory tubercule Neocortex Major systems: Diffuse reticular; Basal forebrain; Intrinsic Nicotinic receptor γ β δ α α Binding site γ β δ α α 7.9 Primary site of action 13 14 15 Sunday, January 9, 2011
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Nicotinic receptor Purifed From electric organs α -bungartoxin Pentameric structure Na+ channel (EPSP) In brain presynaptic Ca 2+ channel increase release γ β δ α α 7.9 Actions on DA systems Ventral tegmental area Locomotor stimulation Nicotine self-administration DA release Striatum Nucleus accumbens Locomotor activity changes DA release Lesions disrupt self-administration 14.4 Dopamine Psychopharmacology , 1992 EFFect oF 6-OHDA lesion on nicotine selF- administration 16 17 18 Sunday, January 9, 2011
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Sedative- Hypnotics (Lec 9 cont ʼ d) Drop one exam of 1-3!!! “Gin Lane”
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181lec9.key - Psych 181: Dr. Anagnostaras Lec 9: Nicotine 1...

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