ENHANCEMENT OF PERFORMANCE IN MULTIPLE LEARNING-TASKS BY CORTICOTROPIN-RELEASING FACTOR-BINDING PROTEIN LIGAND INHIBITORS

Evidence favors a role for corticotropin-releasing factor (CRF) in lea rning and memory processes. A binding protein (CRF-BP) with the abilit y to inactivate CRF provides a novel target to modulate endogenous lev els of CRF. The present studies employed three measures of information processing in rats in order to examine the impact of CRF system activ ation resulting from administration of CRF-BP ligand inhibitors, which increase levels of ''free CRF.'' Acquisition of a visual discriminati on paradigm and retention of a inhibitory avoidance task were dose dep endently facilitated by central administration of a CRF-BP ligand inhi bitor. CRF-BP ligand inhibitor treatment also improved performance in an active avoidance paradigm in aged animals. No nonspecific anorexic effects of the active dose of CRF-BP Ligand inhibitor were detected in a food intake test. Moreover, the magnitude of in vivo efficacy of th r CRF-BP ligand inhibitor peptide in producing a mild increase in moto r activity was dissociated from that of a postsynaptic CRF receptor ag onist that exerted robust and long-lasting activity increases. Thus, C RF-BP ligand inhibitors appear to elicit generalized learning enhancem ent effects without mimicking the robust nonspecific behavioral action s of a CRF receptor agonist. (C) 1997 Elsevier Science Inc.