Chronic cocaine reduces RGS4 mRNA in rat prefrontal cortex and dorsal striatum.
Neuroadaptations affecting dopamine transmission within the prefrontal cortex and striatum are thought to underlie relapse to cocaine seeking after extended periods of abstinence. Regulator of G-protein signaling 4 (RGS4) is a forebrain-enriched protein known to be dynamically regulated by dopamine receptors in response to acute psychostimulant administration. In this report, chronic noncontingent (cocaine binge) or response-contingent (self-administration) delivery of cocaine followed by 2-3 weeks of abstinence resulted in a decrease of RGS4 mRNA in the dorsal striatum and prefrontal cortex. Furthermore, re-exposure to the cocaine-associated context after abstinence renewed the drug seeking and restored the levels of RGS4 mRNA to control values. Changes in RGS4 mRNA levels might signal abnormal receptor G-protein coupling that impacts cocaine seeking.
Schwendt
Marek
M
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Hearing
Matthew C
MC
See
Ronald E
RE
McGinty
Jacqueline F
JF
D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020710:RGS Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D012008:Recurrence; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D018765:Dopamine Uptake Inhibitors; D020710:RGS Proteins; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D043562:Receptors, G-Protein-Coupled; C098799:RGS4 protein; D003042:Cocaine; D004298:Dopamine