NICOTINE INDIRECTLY INHIBITS [H-3] DOPAMINE UPTAKE AT CONCENTRATIONS THAT DO NOT DIRECTLY PROMOTE [H-3] DOPAMINE RELEASE IN RAT STRIATUM

The effects of both (-)- and (+)-nicotine isomers were examined on in vitro uptake and release of [H-3]dopamine in rat striatum. Both isomers inhibited uptake of [H-3]dopamine in chopped tissue at concentrations well below those necessary for promoting release of preloaded [H-3]dopamine. (-)-Nicotine was more potent than (+)-nicotine both at inhibiting uptake and at promoting release. Unlike other dopamine uptake inhibitors, however, nicotine inhibited only 50% of the total uptake. In the presence of 1 nM nicotine, the residual [H-3]dopamine uptake was less sensitive to inhibition by cocaine than uptake in the absence of nicotine. Nicotine did not compete against the binding of [H-3]GBR 12935, a selective dopamine uptake inhibitor. The nicotinic receptor agonists carbachol and 1,1-dimethyl-4-phenylpiperazinium iodide also inhibited uptake, whereas the nicotinic antagonists chlorisondamine and mecamylamine blocked nicotine's effect. Thus, the effect of nicotine on dopamine uptake appears to be mediated by a receptor similar to the nicotinic acetylcholine receptor. These receptors do not seem to be on the terminals that are accumulating dopamine, however, since tetrodotoxin prevented the effect of nicotine on [H-3]dopamine uptake and nicotine had no effect on uptake in a synaptosomal preparation.