Alterations in Fos-Related Antigen 2 and 1 Receptor Gene and Protein Expression Are Associated with the Development of Cocaine-Induced Behavioral Sensitization: Time Course and Regional Distribution Studies

Repeated exposure to cocaine results in neuroadaptations that can alter the way the brain responds to subsequent stimuli. Earlier studies demonstrated that acute administration of co-caine up-regulates the immediate-early gene fos-related anti-gen 2 (fra-2) followed by a later up-regulation of 1 receptor gene and protein levels in brain regions involved in addiction and reward. To test whether such alterations could have long-term consequences on behavior, the present study was under-taken. Using a cocaine-induced behavioral sensitization model coupled with gene and protein expression studies in mice, the results show that cocaine induces the expression of fra-2, which leads to a progressive increase in 1 receptor gene and protein expression over a period of days. This progressive increase in 1 expression corresponds to the steady increas