Selective c-fos induction and decreased dopamine release in the central nucleus of amygdala in rats displaying a mecamylamine-precipitated nicotine withdrawal syndrome.

In the present study the neuronal expression of Fos, the protein product of c-fos, was used to study changes in neuronal activity in nerve terminal regions of the ascending dopaminergic system during nicotine withdrawal. Rats were infused for 14 days with nicotine (9 mg/kg/day nicotine hydrogen tartrate) via minipumps, whereas control animals carried empty pumps. Withdrawal was induced by the nicotinic receptor (nAChR) antagonist mecamylamine (1 mg/kg, s.c.). The behavior of each animal was observed after mecamylamine injection and subsequently its brain was processed for Fos-like immunoreactivity. Following mecamylamine, the score of abstinence signs increased in the nicotine-treated rats as compared to controls. The number of Fos-positive nuclei was substantially increased in the central nucleus of amygdala (CNA) in animals undergoing mecamylamine-precipitated withdrawal, whereas no significant changes in c-fos expression were observed in the basolateral amygdaloid nucleus, the core and the shell of the nucleus accumbens, the dorsolateral striatum, or the medial prefrontal cortex. Since there are indications of involvement of amygdaloid dopaminergic neurotransmission in anxiety-a core symptom of withdrawal from dependence-producing drugs-in a second experiment utilizing microdialysis we examined whether nicotine withdrawal affects dopaminergic neurotransmission in the CNA. Following mecamylamine injection, dopamine (DA) significantly decreased in nicotine-treated animals compared with controls. These results indicate that the mecamylamine-precipitated nicotine withdrawal reaction is accompanied by a selective induction of c-fos and a concurrent decrease in DA release in the CNA, which may have a bearing on symptoms such as anxiety and distress, which frequently are associated with the nicotine abstinence reaction in humans. Copyright 2000 Wiley-Liss, Inc.