On the action of nicotine and cotinine on central 5-hydroxytryptamine neurons.

The actions of nicotine, and its main metabolite cotinine, on 5-hydroxytryptamine (5-HT) neurons in the brain of the rat have been assessed biochemically (on turnover, uptake, release, overflow and binding of 5-HT in brain) and functionally (on extensor reflex activity, which is 5-HT dependent). Nicotine and cotinine in repeated doses of 2 mg/kg caused a reduction of brain 5-HT turnover, which was not blocked by pretreatment with mecamylamine, and nicotine sifnificantly inhibited the effects of norfenfluramine and 5-methoxydimethyltryptamine on extensor reflex activity, effects counteracted by mecamylamine. In low concentrations cotinine weakly inhibits the uptake and retention of 5-HT and also increases its spontaneous release in vitro. The biochemical findings suggest that the reduction of 5-HT and also increases its spontaneous release in vitro. The biochemical findings suggest that the reduction of 5-HT turnover caused by high doses of nicotine are mediated, at least in part, by its main metabolite cotinine. The experiments on extensor reflexes indicate that nicotine can block the functional expression of 5-HT receptor activity in the spinal cord by an action beyond the 5-HT receptor at nicotine-like cholinergic receptors whose location is also discussed.