Effect of corticotropin-releasing factor antagonist on behavioral and neuroendocrine responses during exposure to defensive burying paradigm in rats.
Defensive burying behavior is a coping strategy in rodents in response to an aversive stimulus where fear will facilitate burying and treatment with anxiolytics will result in less burying. To test the hypothesis that endogenous corticotropin-releasing factor (CRF) is involved in the defensive burying response, the effects of an ICV CRF antagonist were tested on defensive burying behaviors as well as the plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone response. Rats were allowed to self-administer one mild electric shock (1.0 mA) through a probe mounted on the wall of the home cage by briefly touching it. Following this shock, control rats typically display burying behavior, as defined as moving the bedding material toward and/or over the shock probe. A CRF antagonist, alpha-hel CRF9-41, was administered ICV (1, 5, and 25 micrograms) 1 min after they received the shock. The 5 micrograms dose of the CRF antagonist significantly attenuated the time spent in defensive burying compared to vehicle-treated controls. The 5 and 25 micrograms doses of alpha-hel CRF9-41 increased the latency to display defensive burying. However, the enhanced release of plasma ACTH and plasma corticosterone concentrations in the stressed animals was not significantly modified over the 15-min period by either of the three doses of CRF antagonist. The results suggest that endogenous CRF is involved in the expression of defensive burying behavior and that the brain CRF receptors modulating the behavioral response may be different from the CRF receptors modulating the hormonal response of defensive burying.
Korte
S M
SM
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Korte-Bouws
G A
GA
Bohus
B
B
Koob
G F
GF
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000502:physiology
D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C045089:corticotropin releasing hormone (9-41); D003345:Corticosterone