Reversing cocaine-induced synaptic potentiation provides enduring protection from relapse

• DOI: 10.1073/pnas.1011265108
• Publication Date: 2010-12-21T04:23:52Z
• Authors: Khaled Moussawi; Wenhua Zhou; Haowei Shen; Carmela M. Reichel; Ronald E. See; David B. Carr; Peter W. Kalivas
• Keywords: Patch-Clamp Techniques; Microdialysis; Long-Term Potentiation; Glutamic Acid; Prefrontal Cortex; Receptors, Metabotropic Glutamate; Synaptic Transmission; Nucleus Accumbens; Acetylcysteine; Rats; Cocaine-Related Disorders; 03 medical and health sciences; 0302 clinical medicine; Secondary Prevention; Animals; Homeostasis; Chromatography, High Pressure Liquid; Signal Transduction

Cocaine addiction remains without an effective pharmacotherapy and is characterized by inability of addicts to inhibit relapse drug use. Vulnerability arises from enduring impairment in cognitive control motivated behavior, manifested part dysregulated synaptic potentiation extracellular glutamate homeostasis the projection prefrontal cortex nucleus accumbens. Here we show rats trained self-administer cocaine that cocaine-induced changes are mechanistically linked through group II metabotropic receptor signaling. The measures cortico-accumbens glial transmission were restored predrug parameters for at least 2 wk after discontinuing chronic treatment with cystine prodrug, N -acetylcysteine. -acetylcysteine produced these inducing restoration nonsynaptic glutamatergic tone onto receptors. long-lasting pharmacological adaptations also caused inhibition cocaine-seeking animal model relapse. These data link excitatory demonstrate a mechanism chronically restore accumbens thereby model.