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.
Torregrossa
Mary M
MM
Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA. mary.torregrossa@yale.edu
Tang
X-C
XC
Kalivas
Peter W
PW
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003042:Cocaine