Dopamine D-3 receptors modulate evoked dopamine release from slices of ratnucleus accumbens via muscarinic receptors, but not from the striatum

It is not clear whether dopamine D-3 receptor contributes to the regional d ifference in dopamine antagonist-induced increase in the evoked dopamine re lease from the nucleus accumbens and striatum. We investigated the regional differences in augmentation of electrically evoked dopamine release induce d by preferential dopamine D-2 or D-3 receptor antagonists from slices of t he rat striatum and nucleus accumbens. Haloperidol, a preferential dopamine D-2 receptor antagonist, enhanced the evoked dopamine release from both th e striatum and nucleus accumbens. Preferential dopamine D-3 antagonists, ci s-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin HCl [(+)-UH23 2] and 5,6-dimethoxy-2-(di-n-propylamine)indan (U-99194A) resulted in a gre ater increase in the evoked dopamine released from the nucleus accumbens co mpared with that from the striatum. Moreover, U-99194A attenuated the quinp irole-induced reduction of evoked dopamine release from the nucleus accumbe ns but not from the striatum. When slices were superfused with pirenzepine, a muscarinic receptor antagonist, the increase in the evoked dopamine rele ase by (+)-UH232 or U-99194A was reduced in the nucleus accumbens to the sa me level as that in the striatum. Our results indicate that the preferentia l D-3 receptor antagonists-induced increase in evoked dopamine release is p robably mediated by the cholinergic system in the nucleus accumbens, which contains more postsynaptic dopamine D-3 receptors than the striatum.