GABAergic projection from nucleus accumbers to ventral pallidum mediates dopamine-induced sensorimotor gating deficits of acoustic startle in rats

Abstract

Previous studies have demonstrated that increased mesolimbic dopamine (DA) activity disrupts sesorimotor gating as measured by prepulse inhibition (PPI)_of the acoustic startle response (ASR) in rats. Other behavioral changes following mesolimbic DA activation are mediated through GABAergic efferent projections from the nucleus accumbens (NAC) to the pallidum (VP). In this experiment, we examined whether PPI deficits in rats following mesolimbic DA activation mediated through these GABAergic subtances. PPI was significantly disrupted in the rats following infusion of DA (40 μg) into the NAC, and this effect was reversed by infusion of a low dose (10 ng) of the GABA agonist muscimol into the VP. In a second experiment, we tested the hypothesis and the loss of PPi following intra-NAC DA infusion results from a disruption of GABAergic activity within the VP. Consistent with this hypotheasis, infusion of the GABA antagonist picrotoxin (0–0.2 μg) into the VP caused a significant loss of PPI. These findings strongly suggest that the accumbens-ventralk pallidal GABAergic circiutry is a subtance for the decrease in sensorimotor gating induced by mesolimbic DA overativity.