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
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Behavior, Addictive / genetics
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Behavior, Addictive / metabolism
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Behavior, Addictive / physiopathology
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Cocaine / pharmacology*
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Cocaine-Related Disorders / genetics
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Cocaine-Related Disorders / metabolism*
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Cocaine-Related Disorders / physiopathology
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Disease Models, Animal
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Dopamine / metabolism
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Dopamine Uptake Inhibitors / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Drug Administration Schedule
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Male
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Neostriatum / drug effects*
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Neostriatum / metabolism
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Neostriatum / physiopathology
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Prefrontal Cortex / drug effects*
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Prefrontal Cortex / metabolism
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Prefrontal Cortex / physiopathology
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RGS Proteins / genetics*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Dopamine / metabolism
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Receptors, G-Protein-Coupled / drug effects
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Receptors, G-Protein-Coupled / metabolism
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Recurrence
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Self Administration
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Substance Withdrawal Syndrome / genetics
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Substance Withdrawal Syndrome / metabolism
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Substance Withdrawal Syndrome / physiopathology
Substances
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Dopamine Uptake Inhibitors
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RGS Proteins
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RNA, Messenger
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Receptors, Dopamine
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Receptors, G-Protein-Coupled
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RGS4 protein
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Cocaine
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Dopamine