Central administration of corticotropin releasing factor induces long-term sensitization to d-amphetamine

Abstract

Corticotropin releasing factor (CRF) has been shown to initiate neuroendocrine and behavioral to stree. As stress and amphetamine (AMPH) show cross-sensitization, we investigated the role of endogenous CRF in behavioral sensitization to d-AMPH. In order to evaluate the participation of the central action and the pituitary-adrenocortical (PA) stimulatory effect of CRF, we compared the effects of repeated intracerebroventricular (i.c.v.) administration of CRF (0, 0.5, 2.5 μg/2 μl), which have central and neuroendocrine consequences, with those of repeated subcutaneous admistration of CRF (0, 0.1, 0.5, 2.5 μg/250 μl), doses which only stimulate the PA axis, on the development of sensitization to AMPH-induced motor activation administered 1 week later. Repeated i.c.v. administration of CRF induced a long-lasting enhancement of the hyperactivity by 0.75 mg/kg peripheral administration of d-AMPH, whereas no sensitization to d-AMPH was observed following repeated subcutaneous administration of CRF. These results favor the hypothesis that a centrally mediated action of CRF is involved in the cross-sensitization of psychostimulants and stress.