Xb. Wang et al., RG-BETA(1) - A PSYCHOSTIMULANT-REGULATED GENE ESSENTIAL FOR ESTABLISHING COCAINE SENSITIZATION, The Journal of neuroscience, 17(15), 1997, pp. 5993-6000
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.