Interrupted expression of NAC-1 augments the behavioral responses to cocaine

NAC-1 is an mRNA that is increased selectively in the nucleus accumbens aft er acute and repeated cocaine administration. Antisense or control oligonuc leotides were microinjected into the nucleus accumbens of rats to define th e role of NAC-1 in the behavioral responses to acute systemic cocaine. Anti sense oligonucleotides decreased NAC-1 mRNA levels by 26% and markedly enha nced the motor stimulant response to an acute cocaine injection compared to sense oligonucleotide microinjections. The augmentation in cocaine motor b ehavior produced by NAC-1 antisense pretreatment in the nucleus accumbens w as not associated with increased dopamine release as estimated by microdial ysis. In contrast, the behavioral response to dopamine microinjection into the nucleus accumbens was increased after antisense oligonucleotide treatme nt, while the motor response to mu-opioid receptor stimulation was unaltere d. These data suggest that the induction of NAC-1 by cocaine may be a compe nsatory mechanism that minimizes the behavioral impact of cocaine administr ation by regulating postsynaptic dopamine transmission within the nucleus a ccumbens. (C) 1999 Wiley-Liss, Inc.