Dissociation of arousal-like from anxiogenic-like actions of brain corticotropin-releasing factor receptor ligands in rats

Behavioral actions of centrally administered corticotropin-releasing factor (CRF) are likely subserved by multiple brain targets and functional effect or systems. The present studies compared effects of two CRF ligands, a full , post-synaptic CRF receptor agonist (rat/human CRF(1-41)) and a CRF bindin g protein ligand inhibitor (rat/human CRF(6-33)) in a behavioral testing ba ttery sensitive to arousal, fear-like and aversive processes in Wistar rats . The profile of global efficacy for the centrally administered CRF recepto r agonist was characterized by low dose (0.5-1.0 mug) arousal-like effects in locomotor and conditioned ambulation contexts and by high dose (5-25 mug ) conditioned immobility, taste aversion and place aversion. In contrast, a profile of limited efficacy for the centrally administered CRF binding pro tein ligand inhibitor included only dose dependent motor activating and fac ilitation of fear conditioning effects without any of the anxiogenic-like o r aversive properties of CRF agonist administration. These results suggest that arousal-like activation is a fundamental, physiologically relevant con sequence of brain CRF system stimulation whereas aversive and anxiety-like effects reflect pharmacological actions of a CRF receptor agonist. (C) 2001 Elsevier Science B.V. All rights reserved.