Environmental novelty differentially affects c-fos mRNA expression inducedby amphetamine or cocaine in subregions of the bed nucleus of the stria terminalis and amygdala

The environmental context in which amphetamine or cocaine are administered modulates both their acute psychomotor activating effects and their ability to induce sensitization. Here we report that environmental context differe ntially affects patterns of amphetamine- and cocaine-induced c-fos mRNA exp ression in the bed nucleus of the stria terminalis (BST) and amygdala of ma le rats. In the medial amygdala and medial posterior BST, exposure to novelty result ed in a marked increase in c-fos mRNA. Amphetamine given at home did not in duce c-fos mRNA, and when given in the novel environment, did not increase levels beyond that observed for novelty alone. In the basolateral and later al amygdala, amphetamine or cocaine at home or exposure to novelty induced c-fos mRNA. When amphetamine or cocaine was given in a novel environment th e c-fos mRNA response was significantly enhanced. In the central nucleus of the amygdala (CEA) and oval subnucleus of the BST (BSTov), amphetamine adm inistration at home produced a robust increase in c-fos mRNA expression, wh ereas exposure to novelty had little effect. In contrast to other brain reg ions examined, the c-fos mRNA response to amphetamine in a novel versus hom e environment was significantly smaller. In both "home" and "novel" ampheta mine groups, c-fos mRNA in the BSTov and CEA was predominantly expressed in enkephalin-containing cells; coexpression with corticotropin-releasing hor mone was rare. These data suggest that the context in which psychostimulants are given pow erfully and differentially alters the response of limbic structures that ha ve been functionally implicated in drug reinforcement and emotional behavio rs.