Regionally specific effects of acute and chronic nicotine on rates of catecholamine and 5-hydroxytryptamine synthesis in rat brain.
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.
Mitchell
S N
SN
Department of Psychology, Institute of Psychiatry, London, U.K.
Brazell
M P
MP
Joseph
M H
MH
Alavijeh
M S
MS
Gray
J A
JA
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
D002395:Catecholamines; D006584:Hexamethonium Compounds; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D008464:Mecamylamine; D009538:Nicotine