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 effector 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 binding protein ligand inhibitor (rat/human CRF(6-33)) in a behavioral testing battery sensitive to arousal, fear-like and aversive processes in Wistar rats. The profile of global efficacy for the centrally administered CRF receptor agonist was characterized by low dose (0.5-1.0 microg) arousal-like effects in locomotor and conditioned ambulation contexts and by high dose (5-25 microg) conditioned immobility, taste aversion and place aversion. In contrast, a profile of limited efficacy for the centrally administered CRF binding protein ligand inhibitor included only dose dependent motor activating and facilitation of fear conditioning effects without any of the anxiogenic-like or aversive properties of CRF agonist administration. These results suggest that arousal-like activation is a fundamental, physiologically relevant consequence of brain CRF system stimulation whereas aversive and anxiety-like effects reflect pharmacological actions of a CRF receptor agonist.
Heinrichs
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Department of Psychology, Boston College, McGuinn Hall, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. stephen.heinrichs@bc.edu
Joppa
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D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001362:Avoidance Learning / Q000187:drug effects; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003213:Conditioning, Psychological / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects*; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists*
D002352:Carrier Proteins; D008024:Ligands; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D003346:Corticotropin-Releasing Hormone