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

Abstract

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 cocaineinduced 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.

Extinction circuits for fear and addiction overlap in prefrontal cortex

“…Medium spiny neurons projecting from the core to the pallidum express enkephalin (Zahm et al 1985), which, when released during high frequency firing, could stimulate pallidal m opiod receptors (Waldhoer et al 2004) causing a reduction in local GABA levels and reduced inhibition within the pallidum Schroeder and Schneider 2002). Indeed, a m opiod-dependent decrease in pallidal GABA is necessary for cocaine relapse (Tang et al 2005), an effect likely mediated through co-release of enkephalin in the accumbens core-pallidal pathway (Torregrossa et al 2008). Thus, PL-mPFC projections through core to the pallidum could conceivably activate drug seeking.…”

Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior

“…Dopamine projections from the VTA to the nucleus accumbens, mPFC, and basolateral amygdala also seem to be involved in reinstatement. Specifically, dopamine acting on D1 receptors would be capable of stimulating glutamate projection neurons in the amygdala and mPFC Alleweireldt et al, 2006;Schmidt et al, 2009;See, 2009), whereas dopamine acting on both D1 and D2 receptors in the nucleus accumbens shell (Anderson et al, 2003;Bachtell et could act in concert with AMPA receptors to reduce GABAergic transmission to the ventral pallidum, which has been shown to be important in reinstatement (O'Connor, 2001;Torregrossa et al, 2008).…”

The hypothalamus and the neurobiology of drug seeking

“…For example, functional inactivation of dmPFC or AcbCo blocks reinstatement of cocaine seeking elicited by cocaine prime [82] or footshock stress [83]. AcbCo is thought to mediate drug seeking via projections to ventral pallidum [82,84]. The importance of this cortical-striatal-pallidal pathway in drug seeking is well documented [85].…”