We studied the effects of nicotine and epibatidine given in combination with dopamine uptake inhibitor, nomifensine, on striatal extracellular dopamine and its metabolites by using brain microdialysis in freely moving rats. Nomifensine (3 mg/kg) elevated extracellular dopamine in the caudate-putamen, and clearly more in the nucleus accumbens. In the caudate-putamen, nicotine (0.5 mg/kg) and epibatidine (0.6 mu g/kg but not 3.0 mu g/kg) enhanced nomifensine's effect on dopamine. The effect of nomifensine on accumbal dopamine was enhanced by nicotine, but inhibited by epibatidine at 0.6 mu g/kg. The larger dose of epibatidine had no effect. Thus, the effects of the smaller epibatidine dose (0.6 mu g/kg) on the dopamine output in the caudate-putamen but not in the accumbens resemble those of nicotine 0.5 mg/kg. Discrepancies in the effects of epibatidine and nicotine are most probably due to differences in their affinities to nicotinic receptor subtypes regulating dopamine release. Further, different responses to low concentrations of epibatidine between the brain areas suggest that there are differences in the nicotinic regulation of nigrostriatal and mesolimbic dopaminergic pathways. (c) 2005 Elsevier B.V. All rights reserved.
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