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Volume 17, Number 15, Issue of August 1, 1997 pp. 5993-6000
Copyright ©1997 Society for Neuroscience

rG₁: A Psychostimulant-Regulated Gene Essential for Establishing Cocaine Sensitization

Received Feb. 7, 1997; revised May 15, 1997; accepted May 20, 1997.

Xiao-Bing Wang¹, Masahiko Funada¹, Yasuo Imai¹, Randal S. Revay¹, Hiroshi Ujike¹, David J. Vandenbergh¹, and George R. Uhl^{1, 2}

¹ Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, and ² Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224

Repeated doses of cocaine or amphetamine lead to long-lasting behavioral manifestations that include enhanced responses termed sensitization. Although biochemical mechanisms that underlie these manifestations currently remain largely unknown, new protein synthesis has been implicated in several of these neuroadaptive processes. To seek candidate biochemical mechanisms for these drug-induced neuroplastic behavioral responses, we have used an approach termed subtracted differential display (SDD) to identify genes whose expression is regulated by these psychostimulants. rG₁ is one of the SDD products that encodes a rat G-protein  subunit. rG₁ expression is upregulated by cocaine or amphetamine treatments in neurons of the nucleus accumbens shell region, a major center for psychostimulant effects in locomotor control and behavioral reward. Antisense oligonucleotide treatments that attenuate rG₁ expression in regions including the nucleus accumbens abolish the development of behavioral sensitization when they are administrated during the repeated cocaine exposures that establish sensitization. These treatments fail to alter acute behavioral responses to cocaine, and they do not block the expression of cocaine sensitization when it is established before oligonucleotide administrations. Full, regulated rG₁ expression is a biochemical component essential to the establishment of a key consequence of repeated cocaine administrations, sensitization.

Key words: PCR differential display; amphetamine; cocaine; G-protein; sensitization; gene regulation; addiction

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