Evidence for a selective prefrontal cortical gabab receptor-mediated inhibition of glutamate release in the ventral tegmental area: A dual probe microdialysis study in the awake rat

Intra-mPfc KCl transiently increased VTA glutamate release (+71.48±14.29%, 20 min). Intra-mPfc perfusion with a concentration of the GABAA receptor antagonist bicuculline (10 μM, 120 min) did not influence the intra-mPfc KCl-induced increase in VTA glutamate release (+102.35±33.61%, 20 min). In contrast, intra-mPfc perfusion with a concentration of the GABAB receptor antagonist CGP35348 (100 μM, 120 min) which when given alone did not influence basal glutamate levels in the VTA was associated with an enhanced KCl-induced stimulation of VTA glutamate release (+375.19±89.69%, 40 min). Furthermore, this enhancement was reversed in the presence of the selective GABAB receptor agonist baclofen (10 μM, 120 min). The present findings suggest a key role for the prefrontal cortex in the regulation of glutamate release in the VTA. Furthermore, we demonstrate a selective cortical GABAB receptor-mediated inhibition of glutamate transmission in the VTA. These findings may be important in the context of abnormalities in amino acid neurotransmission at the network level in schizophrenia.