D1-D2 dopamine receptor interaction within the nucleus accumbens mediates long-loop negative feedback to the ventral tegmental area (VTA)

The objective of the present study was to examine the effects of perfusion of dopamine (DA) D1- and D2-like receptor agonists in the nucleus accumbens (ACB) on the long-loop negative feedback regulation of mesolimbic somatodendritic DA release in the ventral tegmental area (VTA) of Wistar rats employing ipsilateral dual probe in vivo microdialysis. Perfusion of the ACE for 60 min with the D1-like receptor agonist SKF 38393 (SKF, 1-100 muM) dose-dependently reduced the extracellular levels of DA in the ACE, whereas the extracellular levels of DA in the VTA were not changed. Similarly, application of the D2-like receptor agonist quinpirole (Quin, 1-100 muM) through the microdialysis probe in the ACE reduced the extracellular levels of DA in the ACE in a concentration-dependent manner, whereas extracellular levels of DA in the VTA were not altered. Go-application of SKF (100 muM) and Quin (100 muM) produced concomitant reductions in the extracellular levels of DA in the ACE and VTA. The reduction in extracellular levels of DA in the ACE and VTA produced by co-infusion of SKF and Quin was reversed in the presence of either 100 muM SCH 23390 (D1-like antagonist) or 100 muM sulpiride (D2-like antagonist). Overall, the results suggest that (a) activation of dopamine D1- or D2-like receptors can independently regulate local terminal DA release in the ACE, whereas stimulation of both subtypes is required for activation of the negative feedback pathway to the VTA.