Propranolol antagonizes the enhanced conditioned fear produced by corticotropin releasing factor.
A series of experiments examined the effects of systemic administration of the beta adrenergic antagonist propranolol on the enhanced conditioned fear and the locomotor hyperactivity induced by central administration of corticotropin releasing factor (CRF). In Experiment 1, CRF (0.5 microgram) was shown to reduce responding in both the conditioned stimulus (cs) and the pre-cs components of an on-the-base-line conditioned suppression schedule. The effects of CRF on cs, but not pre-cs responding were antagonized by propranolol, at doses (2.5, 5.0 and 10.0 mg/kg) that did not affect responding themselves. This reversal of the anxiogenic effects of CRF by propranolol was specific to l- and not d-propranolol, showing that it did not result from nonspecific membrane stabilization. Propranolol also failed to reverse the reduced responding induced by the benzodiazepine inverse agonist FG 7142 in this schedule. In Experiment 2, propranolol was shown to potentiate the locomotor hyperactivity induced by CRF in a familiar photocell cage. These results suggest that activation of beta adrenoceptors may be an important mechanism in the behavioral inhibition induced by CRF, and that the neurochemical mechanisms that underlie the "anxiogenic" and the "activating" behavioral effects of CRF are neuropharmacologically distinct.
Cole
B J
BJ
Department of Basic and Clinical Research, Research Institute of Scripps Clinic, La Jolla, California.
Koob
G F
GF
D000818:Animals; D001007:Anxiety / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects*; D005442:Flumazenil / Q000494:pharmacology; D008125:Locus Coeruleus / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013237:Stereoisomerism
D002243:Carbolines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D005442:Flumazenil; C035874:FG 7142; D003346:Corticotropin-Releasing Hormone; D011433:Propranolol