title: Activation of central CRF receptor 1 by cortagine results in enhanced passive coping with a naturalistic threat in mice.
abstract: CRF receptor subtype 1 (CRF1), abundantly expressed in the central nervous system, has been implicated in defensive behavior in rodents. Pharmacological activation of CRF1 by peptidic agonists results in enhancement of anxiety-like behavior. However, receptor specificity of commonly used agonists was confounded by significant affinity to other receptors and widely used laboratory tests of experimental anxiety suffer from artificial aversive stimulation (e.g. electric shock), and limited measures of anxiety-like behavior. We used the recently developed, CRF1-selective agonist cortagine in a mouse model of defensive behaviors under semi-natural conditions, the rat exposure test (RET). Cortagine was injected bilaterally into the cerebral ventricles (i.c.v.) of male C57Bl/6J mice, 20min before exposure to a rat in specifically designed box that evokes a wide variety of defensive behaviors such as active/passive avoidance, freezing, risk assessment, and burying. Pre-injection of the CRF receptor antagonist acidic astressin was used to test for receptor specificity of the observed cortagine effects. A control experiment with no rat present was performed to test for baseline effects of cortagine in the exposure setup. Cortagine dose-dependently enhanced passive avoidance and freezing while burying was decreased. CRF receptor antagonism reliably blocked the effects of cortagine. Our results confirm previous findings of anxiogenic-like effects of cortagine, and demonstrate the usefulness of the RET in investigating differential pattering of drug-induced anxiety-like behavior in mice. In conclusion, our results suggest that CRF1 activation in forebrain areas promotes passive coping with the natural threat presented in the RET.
authors.affiliation: Specialized Neuroscience Research Program, John A. Burns School of Medicine, University of Hawai'i, 651 Ilalo St, Honolulu, HI 96813, USA. philip.tovote@fmi.ch
authors.forename: Philip
authors.initials: P
authors.lastname: Tovote
authors.forename: Catherine Borna
authors.initials: CB
authors.lastname: Farrokhi
authors.forename: Rachael M K
authors.initials: RM
authors.lastname: Gonzales
authors.forename: Udo
authors.initials: U
authors.lastname: Schnitzbauer
authors.forename: D Caroline
authors.initials: DC
authors.lastname: Blanchard
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Blanchard
authors.forename: Joachim
authors.initials: J
authors.lastname: Spiess
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects*; D000378:Agonistic Behavior / Q000187:drug effects*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists* / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
chemical_list: D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D011993:Recombinant Fusion Proteins; C488590:cortagine; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone