CORTICOTROPIN-RELEASING FACTOR CRF1, BUT NOT CRF2, RECEPTORS MEDIATE ANXIOGENIC-LIKE BEHAVIOR

The recent identification and differential localization in brain of th ree binding sites for corticotropin-releasing factor (CRF)-like peptid es (CRF1 and CRF2 receptors as well as CRF-binding protein) suggest th e existence of functionally distinct neurobiological systems which med iate CRF activation. For instance, evidence from receptor knockdown an d pharmacological studies suggests involvement of the CRF1 receptor in anxiogenic-like behavior and the CRF-binding protein in learning and memory processes. The present studies examined the potential functiona l significance of the CRF2 receptor in relation to the CRF1 receptor u sing two animal models of anxiety and endocrine reactivity to a stress or. CRF1 and CRF2 receptor knockdown was achieved and confirmed autora diographically within brain regions relevant to behavioral reactivity to stressors by chronic, central administration of antisense oligonucl eotides. CRF1, but not CRF2, knockdown produced a significant anxiolyt ic-like effect in the Defensive Withdrawal paradigm relative to vehicl e-treated and two missense oligonucleotide negative control groups. In contrast, neither antisense treatment altered endocrine or behavioral reactivity to a swim stressor. Thus, the present data support the rep orted role of CRF1 receptors in the mediation of anxiogenic-like behav ior and suggest a functionally distinct role for CRF2 receptors in bra in. (C) 1997 Elsevier Science B.V.