Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats

Previous findings indicated differences in neuronal circuitries mediating drug reinforcement between the anterior and posterior ventral tegmental area (VTA). The objective of the present study was to examine the effects of the dopamine D2 antagonist sulpiride and the GABAA antagonist picrotoxin administered in the anterior and posterior VTA on the activity of mesoaccumbal dopamine neurons in female Wistar rats. Sulpiride and picrotoxin were administered in the anterior and posterior VTA. Extracellular dopamine levels were measured in sub-regions of the VTA and nucleus accumbens (ACB). Reverse-microdialysis of sulpiride (100 µM) into the posterior VTA increased extracellular dopamine levels locally (80% above baseline) and in the ACB shell and core (70% above baseline), whereas reverse-microdialysis into the anterior VTA produced a much smaller effect locally (30% above baseline) and in the ACB shell and core. In contrast, microinjection of picrotoxin (80 and 160 µM) into the anterior, but not posterior VTA, increased dopamine release in the ACB shell. The results suggest that dopamine neurons in the posterior VTA, compared to the anterior VTA, may be under greater D2 receptor-mediated tonic inhibition, whereas dopamine neurons in the anterior VTA, compared to the posterior VTA, may be under greater GABAA receptor-mediated tonic inhibition.