Nicotine produces antidepressant-like actions: Behavioral and neurochemical evidence

Converging lines of evidence indicate the involvement of nicotinic acetylcholine receptors in depressive illness and antidepressant drug action. We investigated the effects of sub-chronic and chronic treatment with imipramine, nicotine and their combination on: (a) the ability of a dopamine-mimetic challenge to produce locomotor stimulation and (b) cortical density of β-adrenoceptors. One week of treatment with imipramine (10 mg/kg, twice daily) did not result in an altered response to the apomorphine (0.15 mg/kg) challenge, but after 2 weeks, the imipramine-treated rats demonstrated hyperactivity. Conversely, such increased locomotor response was observed in rats treated with nicotine (0.4 mg/kg, twice daily) for 1 but not for 2 weeks. Groups treated with nicotine + imipramine for 1 and 2 weeks demonstrated equally high hyperactivity in response to the apomorphine challenge. This effect was not different from the effects of 1-week treatment with nicotine or 2-week treatment with imipramine. The density of β-adrenoceptors was equally decreased by 2 (but not 1) weeks of the treatment with imipramine, nicotine and their combination. The present behavioral and neurochemical data suggest the antidepressant-like effect of the chronic treatment with nicotine. It appears that the potentiation of the dopamine-mimetic-induced hyperactivity cannot be explained by β-adrenoceptor down-regulation.