GABA(A) receptor blockade in the anterior ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats

Previously, it was shown that microinfusion of the GABA(A) antagonist picrotoxin into the anterior ventral tegmental area (VTA) is reinforcing. It was hypothesized that this reinforcing effect of picrotoxin in the anterior VTA is mediated, at least in part, by the activation of the mesoaccumbens dopamine (DA) system. The objective of the present study was to determine if blockade of GABA(A) receptors in the anterior VTA can increase extracellular levels of DA in the nucleus accumbens (ACB), using an in vivo microdialysis technique in freely moving rats. Concentrations of picrotoxin (40, 80, and 160 mu M) that had previously been shown to produce a reinforcing effect increased the extracellular levels of DA and its major metabolites in the ACE. The increased extracellular DA levels induced by intra-VTA injection of picrotoxin was markedly attenuated by coadministration with the GABA(A) agonist muscimol,whereas intra-VTA injection of muscimol alone did not have an apparent effect on extracellular DA revels in the ACE. Microinjection of another GABA(A) antagonist, bicuculline, into the anterior VTA also increased the extracellular release of DA in the ACE. These results suggest that DA neurons projecting from the anterior VTA to the ACB are tonically inhibited by GABA through its actions at the GABA(A) receptors.