Effects of pharmacological stressors on c-fos and CRF mRNA in mouse brain: relationship to alcohol seeking.

A marked heterogeneity exists among stressors in their ability to reinstate alcohol seeking in rats. We have reported that the pharmacological stressor yohimbine, an alpha-2 adrenoceptor antagonist, potently reinstated alcohol seeking, but FG-7142, a benzodiazepine inverse agonist was ineffective. In rats, we determined that yohimbine elicits patterns of brain expression of the mRNAs for c-fos, a marker of neuronal activation, and corticotropin-releasing factor (CRF) a stress-related peptide, distinct from that produced by FG-7142. The purpose of the present experiment is to determine if these differential effects of yohimbine and FG-7142 on regional c-fos and CRF mRNA expression generalize to another animal commonly used in alcohol research, the C57 BL/6J mouse. In comparing the results of the present study to those of our previous one, we found a number of commonalities in the patterns of activation elicited by yohimbine and FG-7142 between the two species, and some notable differences. As we found in the rat, yohimbine selectively increased c-fos mRNA in the mouse NACs, BLA and CeA. Yohimbine increased CRF mRNA only in the mouse PVN, but was without effect on CRF mRNA in extrahypothalamic sites, the BNST and CeA. This differs from what we saw in the rat, where yohimbine increased CRF mRNA in these extrahypothalamic regions, but not the PVN. The selective induction of c-fos in the NACs, BLA and CeA of mice and rats by yohimbine offers further support for the idea that activation of these structures participates in reinstatement induced by such stressors.