Dopamine D(3) receptors modulate evoked dopamine release from slices of rat nucleus accumbens via muscarinic receptors, but not from the striatum.

摘要

It is not clear whether dopamine D(3) 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 D(2) or D(3) receptor antagonists from slices of the rat striatum and nucleus accumbens. Haloperidol, a preferential dopamine D(2) receptor antagonist, enhanced the evoked dopamine release from both the striatum and nucleus accumbens. Preferential dopamine D(3) 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 D(3) receptor antagonists-induced increase in evoked dopamine release is probably mediated by the cholinergic system in the nucleus accumbens, which contains more postsynaptic dopamine D(3) receptors than the striatum.