NAC-1, A RAT-BRAIN MESSENGER-RNA, IS INCREASED IN THE NUCLEUS-ACCUMBENS 3 WEEKS AFTER CHRONIC COCAINE SELF-ADMINISTRATION

Chronic cocaine use leads to biochemical and behavioral changes that c an persist for weeks to months after drug administration is discontinu ed. Alterations in gene expression in the mammalian CNS may contribute to these long-term neural consequences of cocaine abuse. A combined i n situ transcription-PCR amplification strategy was used to isolate a novel mRNA, NAC-l,from the nucleus accumbens of rats 3 weeks after dis continuing 3 weeks of intravenous cocaine self-administration. In rats that self-administered cocaine, levels of NAG-I were increased simila r to 50% in the nucleus accumbens but not in the dorsal striatum or hi ppocampus, when compared with levels from yoked-saline controls. in si tu hybridization analysis demonstrated increased numbers of NAC-1-expr essing cells in the nucleus accumbens of rats had self-administered co caine. NAC-1 mRNA exists as one form, similar to 4400 nucleotides (nt) in size, and also is present at much lower amounts in non-neural tiss ues. A full-length cDNA clone was isolated from a whole brain library. The predicted polypeptide sequence contains a POZ domain in the first 120 amino acids; the same POZ domain sequence mediates protein-protei n interactions among some transcriptional regulators, NAC-1 mRNA level s were also increased in the nucleus accumbens 1 week after 6 d of non contingent cocaine treatments. Regulation of NAG-1 mRNA in the nucleus accumbens demonstrates a long-term effect of cocaine use on cellular function that may be relevant in behavioral sensitization or cocaine s elf-administration.