Age Differences in Cocaine-Induced ERK Activation

92197 Age Differences in Cocaine-Induced ERK Activation Mohammad Faiyaz Shaikh Mentor: Frances Leslie Adolescence is characterized by risk-taking behavior such as initiation of drug use. Our lab previously reported that adult and adolescent rats showed differences in acute cocaine-induced c- fos mRNA expression in key brain regions. C-fos expression can be modulated by extracellular signal-regulated kinase (ERK) signaling. Several drugs of abuse show patterns of dopamine D1- receptor dependent ERK activation in limbic brain regions of adult rodents. This study investigated whether age differences in c-fos expression are correlated with age differences in ERK activation in limbic brain regions, such as medial prefrontal cortex (mPFC), striatum, and extended amygdala. Juvenile (P27), adolescent (P37), and adult male Sprague-Dawley rats were injected twice intravenously (one minute interval) with cocaine (750 µg/kg/0.1 ml injection) or saline. After fifteen minutes, animals were perfused and brains were collected. Immunohistochemical techniques were used to quantify the number of phosphorylated ERK (pERK) immunopositive cells. In the mPFC, the dorsal striatum, the shell and core of the nucleus acumbens (NAc), the lateral bed nucleus of the stria terminalis (BNST), and the central nucleus of the amygdala (CeA), adult and adolescent animals showed greater cocaine-induced increase in pERK than juvenile animals. Animals at P27 showed higher baseline activation in the dorsal striatum and the CeA than other ages. Age differences in cocaine-induced pERK are generally correlated with differences in c-fos expression, but deviations exist. Additionally, these findings might explain previously observed age differences in cocaine-seeking behavior.