The recent identification and differential localization in brain of three binding sites for corticotropin-releasing factor (CRF)-like peptides (CRF 1 and CRF 2 receptors as well as CRF-binding protein) suggest the existence of functionally distinct neurobiological systems which mediate CRF activation. For instance, evidence from receptor knockdown and pharmacological studies suggests involvement of the CRF 1 receptor in anxiogenic-like behavior and the CRF-binding protein in learning and memory processes. The present studies examined the potential functional significance of the CRF 2 receptor in relation to the CRF 1 receptor using two animal models of anxiety and endocrine reactivity to a stressor. CRF 1 and CRF 2 receptor knockdown was achieved and confirmed autoradiographically within brain regions relevant to behavioral reactivity to stressors by chronic, central administration of antisense oligonucleotides. CRF 1, but not CRF 2 , knockdown produced a significant anxiolytic-like effect in the Defensive Withdrawal paradigm relative to vehicle-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 reported role of CRF 1 receptors in the mediation of anxiogenic-like behavior and suggest a functionally distinct role for CRF 2 receptors in brain.
Regulatory Peptides – Elsevier
Published: Jul 23, 1997
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