Protein kinase C regulation of dopamine transporter initiated by nicotinic receptor activation in slices of rat prefrontal cortex

We previously reported that activation of nicotinic receptors causes an enhancement in amphetamine-stimulated release of dopamine via its transporter from slices of prefrontal cortex, but no such enhancement of release from slices of nucleus accumbens or striatum. The nicotinic receptors mediating the enhancement most likely contain α4 and β2 subunits based upon pharmacological characterization. In this study, we sought to characterize the second messenger systems associated with the nicotine-mediated response. Sodium channel involvement was confirmed by the observation that tetrodotoxin blocked nicotine-mediated enhancement, whereas veratridine or elevated K+ mimicked the enhancement seen with nicotine. Inclusion of EGTA blocked nicotine-mediated enhancement, suggesting that, even though no exogenous Ca2+ was added, endogenous stores were required for the enhancement. The enhancement by nicotine was also abolished by the L-type voltage-dependent calcium channel (VDCC) antagonist nitrendipine, but not by the N-type VDCC antagonist ω-conotoxin GVIA, Finally, inhibition of protein kinase C also abolished the nicotine-mediated enhancement of amphetamine-stimulated dopamine release, whereas inhibitors of Ca2+/calmodulin kinase II did not. These findings establish that nicotine can exert selective effects on dopamine transporter activity in prefrontal cortex, an area involved in cognition and learning