S(-)-NORNICOTINE INCREASES DOPAMINE RELEASE IN A CALCIUM-DEPENDENT MANNER FROM SUPERFUSED RAT STRIATAL SLICES

The present study demonstrates that S(-)-nornicotine evoked a concentr ation-dependent increase in dopamine (DA) release from superfused rat striatal slices. The increase in DA release was indicated by an S(-)-n ornicotine-induced overflow of endogenous 3,4-dihydroxyphenylacetic ac id (DOPAC) in the striatal superfusate and by an S(-)-nornicotine-indu ced increase in tritium overflow from striatal slices preloaded with [ H-3]DA. Low concentrations (0.01-1.0 muM) of S(-)-nornicotine, which d id not evoke endogenous DOPAC overflow, also were unable to modulate e lectrically evoked DOPAC overflow. The increase in DOPAC overflow indu ced by S(-)-nornicotine was compared with that produced by S(-)-nicoti ne. Comparing equimolar concentrations (0.1-100 muM) of S(-)-nornicoti ne and S(-)-nicotine, superfusion with S(-)nornicotine resulted in a s ignificantly greater DOPAC overflow. In contrast to the effect of S(-) -nicotine, S(-)-nornicotine evoked a sustained increase in DOPAC overf low for the entire period of S(-)-nornicotine exposure. Furthermore, D OPAC overflow evoked by S(-)-nornicotine in control Krebs buffer was i nhibited by superfusion with a low-calcium buffer, Moreover, in the lo w-calcium buffer, DOPAC overflow induced by 30 and 100 muM S(-)-nornic otine was not different from that with no S(-)-nornicotine. The result s indicate that S(-)-nornicotine, a constituent of tobacco products an d a known metabolite of S(-)-nicotine, increases DA release in a calci um-dependent manner in superfused rat striatal slices. It is interesti ng that unlike S(-)-nicotine, there does not appear to be desensitizat ion to this effect of S(-)-nornicotine.