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.