The effect of cotinine on nicotine- and cocaine-induced dopamine release in the nucleus accumbens

Cotinine is the major metabolite of nicotine. Nicotine is rapidly metaboliz ed and has a short half-life, but cotinine is metabolized and eliminated at a much lower rate. Because of the resulting increase with time in the coti nine to nicotine ratio in the body, including in the brain, it is of intere st to examine the effect of cotinine on nicotine-induced changes. In studie s on conscious, freely-moving rats, intravenous administration of either ni cotine or cocaine induced the release of dopamine in the nucleus accumbens, as assayed by microdialysis. Prior intravenous administration of a high do se of cotinine (500 mu g/kg) inhibited this nicotine- or cocaine-induced do pamine release. The action of cotinine does not seem to occur through its e ffect on the metabolism of nicotine or on its binding at the receptor site, because cotinine, unlike nicotine, does not affect the binding of the nico tinic ligand cytisine. The findings suggest that cotinine affects a putativ e component of the reward mechanism, and as such could have therapeutic val ue.