Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921489 | European Journal of Pharmacology | 2005 | 9 Pages |
Abstract
Corticotropin releasing factor (CRF) and Urocortin are important neurotransmitters in the regulation of physiological and behavioral responses to stress. Centrally administered CRF or Urocortin produces anxiety-like responses in numerous animal models of anxiety disorders. Previous studies in our lab have shown that Urocortin infused into the basolateral nucleus of the amygdala produces anxiety-like responses in the social interaction test. Subsequently, in the current study we prepared a specific CRF1 receptor antagonist (N-Cyclopropylmethyl-2,5-dimethyl-N-propyl-N'-(2,4,6-trichloro-phenyl)-pyrimidine-4,6-diamine, NBI3b1996) to examine in this paradigm. This CRF1 receptor antagonist inhibited the ex vivo binding of 125I-sauvagine to rat cerebellum with an ED50 of 6 mg/kg, i.p. NBI3b1996 produced a dose-dependent antagonism of Urocortin-induced anxiety-like behavior in Social Interaction test with an ED50 of 6 mg/kg, i.p. The compound had no effect on baseline social interaction. In addition, the CRF1 receptor antagonist prevented the stress-induced decrease in social interaction. These results provide further support for the CRF1 receptor in anxiety-like behavior and suggest this pathway is quiescent in unstressed animals.
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Authors
Donald R. Gehlert, Anantha Shekhar, S. Michelle Morin, Phillip A. Hipskind, Charity Zink, Susan L. Gackenheimer, Janice Shaw, Stephanie D. Fitz, Tammy J. Sajdyk,