title: Regionally specific effects of acute and chronic nicotine on rates of catecholamine and 5-hydroxytryptamine synthesis in rat brain.
abstract: Acute (-)-nicotine administration (0.4 and 0.8 mg/kg s.c.) produced a regionally specific increase in the rate of catecholamine synthesis in the rat nucleus accumbens, hypothalamus and hippocampus but not elsewhere, including the caudate-putamen. In all regions rates of 5-hydroxytryptamine synthesis were unaffected. (-)-Cotinine (0.4 and 0.8 mg/kg), the major metabolite of (-)-nicotine was without effect. (-)-Nicotine-induced increase in catecholamine synthesis occurred by a direct stimulation of central nicotinic receptors, as mecamylamine (5 mg/kg) but not hexamethonium (5 mg/kg) was an effective antagonist. Following repeated daily injections of (-)-nicotine (0.8 mg/kg) for up to 28 days, the induced catecholamine response following a subsequent challenge was unaffected in the nucleus accumbens and hypothalamus, but was increased in the hippocampus. This effect persisted for up to 14 days following withdrawal. Rates of 5-hydroxytryptamine synthesis remained unaltered after chronic pretreatment.
authors.affiliation: Department of Psychology, Institute of Psychiatry, London, U.K.
authors.forename: S N
authors.initials: SN
authors.lastname: Mitchell
authors.forename: M P
authors.initials: MP
authors.lastname: Brazell
authors.forename: M H
authors.initials: MH
authors.lastname: Joseph
authors.forename: M S
authors.initials: MS
authors.lastname: Alavijeh
authors.forename: J A
authors.initials: JA
authors.lastname: Gray
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000096:biosynthesis*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000096:biosynthesis*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D002395:Catecholamines; D006584:Hexamethonium Compounds; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D008464:Mecamylamine; D009538:Nicotine