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

Abstract

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 GABA(A) 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 microM) 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 microM) 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 GABA(A) receptor-mediated tonic inhibition.

Fig. 1

The placements of microdialysis probes and injection sites in different sub-regions of the VTA and ACB. In the experiments, all probes were implanted in the right hemisphere of rat brains. For illustration convenience, probe placements inthe ACB core and VTA are drawn on the left side.A: The lines represent the 1.5 mm length of microdialysis probesin the ACB shell (right side) and core (left side). B: The lines in brain slices from −4.8 mm to −5.2 mm indicate microdialysis probes in the anterior VTA, and the lines in slices from −5.3 mm to −6.04 mm indicate probes in the posterior VTA. The open circles represent for injection sites within the anterior VTA and the filled triangles for injection sites in the posterior VTA.

Fig. 2

The effects of reverse-microdialysis of 100-µM sulpiride into the anterior and posterior VTA on local extracellular dopamine levels. Time-course plots are corrected for delays due to the length of the inlet and outlet lines. *: significantly higher from baselines, p<0.05. #: significantly higher than the anterior VTA, p<0.05.

Fig. 3

A: Time course of extracellular dopamine levels in the ACB shell and core after perfusing sulpiride into the posterior VTA. *, #: significantly different from baseline level, p<0.05; *: ACB shell data; #:ACB core data. B: Time course of extracellular dopamine levels in the ACB shell and core after perfusing sulpiride into the anterior VTA. *, #: significantly different from baseline level, p«0.05; *: ACB shell data; #: ACB core data.

Fig. 4

The average extracellular dopamine levels in three collection areas during 40- to 100-min reverse-microdialysis of sulpiride into the anterior or posterior VTA. *: significant difference between reverse-microdialysis in the anterior and posterior VTA, p<0.05.

Fig. 5

A: The effects of microinjecting picrotoxin into the anterior VTA on extracellular dopamine levels in the ACB shell. *: significant difference from baseline, p<0.05. #: different from aCSF-injection group, p<0.05; $: different from aCSF- and 80 µM picrotoxin-injection groups, p<0.05. B: The effects of microinjection of picrotoxin into the posterior VTA on extracellular dopamine levels in the ACB shell. There was no significant effect of picrotoxin.