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

Neurosci Lett. 2008 Jun 20;438(2):142-5. doi: 10.1016/j.neulet.2008.04.016. Epub 2008 Apr 10.

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 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / metabolism
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / metabolism
  • Cocaine-Related Disorders / physiopathology
  • Disease Models, Animal
  • Dopamine Uptake Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • GABA Agonists / pharmacology
  • Globus Pallidus / drug effects
  • Globus Pallidus / metabolism
  • Globus Pallidus / physiopathology
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • GABA Agonists
  • Receptors, AMPA
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Cocaine