The glutamatergic projection from the prefrontal cortex to the nucleus accumbens core is required for cocaine-induced decreases in ventral pallidal GABA.

Cocaine-primed reinstatement of drug seeking is associated with a decrease in extracellular GABA in the ventral pallidum (VP). The present study investigated the neural mechanism of this cocaine-induced decrease in VP GABA by determining if activity of the glutamatergic projection from the medial prefrontal cortex (PFC) to the nucleus accumbens is required for the effect. Microdialysis was performed to measure extracellular GABA in the VP while simultaneously, either a combination of the GABA agonists baclofen and muscimol was microinjected into the PFC, or the AMPA/kainate glutamate receptor antagonist CNQX was microinjected into the accumbens core. Inhibition of the PFC with GABA agonists and blockade of AMPA glutamate receptors in the accumbens core were both sufficient to prevent the cocaine-induced decrease in VP GABA, further implicating increased activity of the cortico-striato-pallidal circuit in relapse to drug seeking.