Role of corticotropin releasing factor (CRF) receptors 1 and 2 in CRF-potentiated acoustic startle in mice.
BACKGROUND
Hypersecretion of corticotropin releasing factor (CRF) has been implicated in both severe anxiety disorders and major depression. Although the role of the CRF1 receptor in the anxiogenic effects of CRF is well supported, the role of CRF2 receptors in anxiety-like behaviors is less clear. In rats, CRF increases the acoustic startle reflex (ASR) via its action in the extended amygdala, providing a putative measure of CRF-mediated anxiogenic activity.


OBJECTIVE
To characterize the effect of CRF on ASR in mice and determine the respective roles of CRF1 and CRF2 receptors in CRF-potentiated ASR.


METHODS
The present study examined: (1) the time course and dose response functions for the effects of human/rat (h/r)-CRF (0.02-0.6 nmol, ICV (intracerebroventricular)) on ASR in two inbred strains of mice; (2) the effects of the CRF1 receptor antagonist NBI-30775 (20 mg/kg, intraperitoneal) and the CRF2 receptor antagonist Antisauvagine-30 (1-10 nmol, ICV) on CRF-potentiated ASR and (3) the effects of the CRF2 receptor agonist urocortin 2 (0.2-6 nmol, ICV) on ASR in mice.


RESULTS
h/r-CRF significantly increased ASR in mice in a time-dependent manner with maximal efficacy at the 0.2 and 0.6 nmol doses. 129S6/SvEvTac mice exhibited a slightly increased duration of action and lower minimal effective dose threshold for CRF effects on ASR compared to C57BL/6J mice. Both selective CRF1)and CRF2)antagonists attenuated h/r-CRF-potentiated ASR without affecting acoustic startle when given alone. The selective CRF2 receptor agonist urocortin 2 increased ASR (1 and 2 nmol), albeit with less efficacy than the non-selective CRF receptor agonist h/r-CRF.


CONCLUSIONS
Both CRF1 and CRF2 receptors appear to contribute to the h/r-CRF-induced increases in ASR in mice. These data support the hypothesis that both receptors contribute to the anxiogenic effects of CRF.
Risbrough
Victoria B
VB
Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, Mail Code 0804, La Jolla, CA 92093-0804, USA.
Hauger
Richard L
RL
Pelleymounter
Mary Ann
MA
Geyer
Mark A
MA
D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors; D054832:Urocortins; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D010446:Peptide Fragments; D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C116607:antisauvagine 30; C518358:urocortin 2, mouse; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone