Abstract

It is not clear whether dopamine D₃ receptor contributes to the regional difference in dopamine antagonist-induced increase in the evoked dopamine release from the nucleus accumbens and striatum. We investigated the regional differences in augmentation of electrically evoked dopamine release induced by preferential dopamine D₂ or D₃ receptor antagonists from slices of the rat striatum and nucleus accumbens. Haloperidol, a preferential dopamine D₂ receptor antagonist, enhanced the evoked dopamine release from both the striatum and nucleus accumbens. Preferential dopamine D₃ antagonists,cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin HCl [(+)-UH232] and 5,6-dimethoxy-2-(di-n-propylamine)indan (U-99194A) resulted in a greater increase in the evoked dopamine released from the nucleus accumbens compared with that from the striatum. Moreover, U-99194A attenuated the quinpirole-induced reduction of evoked dopamine release from the nucleus accumbens but not from the striatum. When slices were superfused with pirenzepine, a muscarinic receptor antagonist, the increase in the evoked dopamine release by (+)-UH232 or U-99194A was reduced in the nucleus accumbens to the same level as that in the striatum. Our results indicate that the preferential D₃ receptor antagonists-induced increase in evoked dopamine release is probably mediated by the cholinergic system in the nucleus accumbens, which contains more postsynaptic dopamine D₃receptors than the striatum.