Comparison of the effects of nicotine and epibatidine on the striatal extracellular dopamine

We compared the effects of nicotine and epibatidine on striatal extracellular dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), by microdialysis in freely moving rats. Nicotine (0.5 mg/kg) elevated dopamine in the caudate-putamen and somewhat more in the nucleus accumbens. Epibatidine at 0.3 microg/kg reduced, and at 0.6 and 1.0 microg/kg increased, dopamine in the caudate-putamen; 2.0 and 3.0 microg/kg had no effect. Accumbal dopamine epibatidine elevated only at 3.0 microg/kg. Thus, in contrast to nicotine, epibatidine increased dopamine output in the caudate-putamen at smaller doses than in the accumbens. Both epibatidine and nicotine enhanced accumbal dopamine metabolism clearly more than that in the caudate-putamen. Also epibatidine was found to elevate 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens at smaller doses than in the caudate-putamen. Similarly to what has been reported concerning nicotine, the dose-response curve of epibatidine to increase the dopamine output in the caudate-putamen was bell-shaped and clearly differed from that in the accumbens. These findings indicate that the nicotinic mechanisms controlling dopamine release and metabolism in the nigrostriatal and mesolimbic dopaminergic pathways differ fundamentally.