Chronic cocaine reduces RGS4 mRNA in rat prefrontal cortex and dorsal striatum

Neuroreport. 2007 Aug 6;18(12):1261-5. doi: 10.1097/WNR.0b013e328240507a.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Addictive / genetics
  • Behavior, Addictive / metabolism
  • Behavior, Addictive / physiopathology
  • Cocaine / pharmacology*
  • Cocaine-Related Disorders / genetics
  • Cocaine-Related Disorders / metabolism*
  • Cocaine-Related Disorders / physiopathology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Uptake Inhibitors / pharmacology
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Drug Administration Schedule
  • Male
  • Neostriatum / drug effects*
  • Neostriatum / metabolism
  • Neostriatum / physiopathology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology
  • RGS Proteins / genetics*
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / metabolism
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism
  • Recurrence
  • Self Administration
  • Substance Withdrawal Syndrome / genetics
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Dopamine Uptake Inhibitors
  • RGS Proteins
  • RNA, Messenger
  • Receptors, Dopamine
  • Receptors, G-Protein-Coupled
  • RGS4 protein
  • Cocaine
  • Dopamine