RG-BETA(1) - A PSYCHOSTIMULANT-REGULATED GENE ESSENTIAL FOR ESTABLISHING COCAINE SENSITIZATION

Repeated doses of cocaine or amphetamine lead to longlasting behaviora l manifestations that include enhanced responses termed sensitization. Although biochemical mechanisms that underlie these manifestations cu rrently remain largely unknown, new protein synthesis has been implica ted in several of these neuroadaptive processes. To seek candidate bio chemical mechanisms for these drug-induced neuroplastic behavioral res ponses, we have used an approach termed subtracted differential displa y (SDD) to identify genes whose expression is regulated by these psych ostimulants. rG beta(1), is one of the SDD products that encodes a rat G-protein beta subunit. rG beta(1) expression is upregulated by cocai ne or amphetamine treatments in neurons of the nucleus accumbens shell region, a major center for psychostimulant effects in locomotor contr ol and behavioral reward. Antisense oligonucleotide treatments that at tenuate rG beta(1) expression in regions including the nucleus accumbe ns abolish the development of behavioral sensitization when they are a dministrated during the repeated cocaine exposures that establish sens itization. These treatments fail to alter acute behavioral responses t o cocaine, and they do not block the expression of cocaine sensitizati on when it is established before oligonucleotide administrations. Full , regulated rG beta(1) expression is a biochemical component essential to the establishment of a key consequence of repeated cocaine adminis trations, sensitization.