Contributory role for nornicotine in nicotine neuropharmacology: nornicotine-evoked [3H]dopamine overflow from rat nucleus accumbens slices.

摘要: Nornicotine is a tobacco alkaloid and an active nicotine metabolite, which accumulates in brain to pharmacologically relevant concentrations following repeated administration rats. Furthermore, nornicotine self-administered by rats, indicating that it has reinforcing efficacy may contribute dependence. Since drugs of abuse activate the mesolimbic dopamine (DA) system produce rewarding effects, present study tested hypothesis evokes DA release from nucleus accumbens nicotinic receptor-mediated manner. Rat slices were preloaded with [3H]DA superfused for 60 min absence presence range concentrations. Superfusate samples collected alkaloid-evoked [3H]overflow was determined. S(-)-Nornicotine (EC(50) value = 3.0 microM), R(+)-nornicotine 0.48 S(-)-nicotine 70 nM) evoked concentration-dependent For each enantiomer, 0.3 microM lowest concentration evoke significant [3H]overflow. Dihydro-beta-erythroidine (DHbetaE, 10 classical receptor antagonist, inhibited S(-)-nornicotine-evoked [3H]overflow, involvement receptors. effect S(-)-nornicotine calcium-dependent, consistent mechanism. Whereas found previously be more potent striatum, than its enantiomer accumbens, suggesting different subtypes these regions. Thus, results current indicate stimulated manner, further supporting contributes