210. CRF 1 receptor antagonists as novel putative antidepressants and anxiolytics

Abstract

There is considerable evidence that CRF hypersecretion occurs in patients with major depression and to a lesser extent in certain anxiety disorders. These findings have led to the study of CRF1 receptor antagonists as a putative novel class of antidepressants/anxiolytic. This presentation will summarize the effects of a CRF1 receptor antagonist in a variety of well-characterized preclinical models predictive of clinical efficacy. The main findings we have recently obtained with a novel CRF1 receptor antagonist include: 1) attenuation of the ACTH and corticosterone response in the rate after exposure to swim stress; 2) attenuation of naltrexone-precipitated withdrawal in morphine dependent rats; 3) anxiolytic activity in rats in the open field paradigm; 4) attenuation of flumazanil-precipitated withdrawal in lorazepam-dependent rats; 5) increased time that rhesus monkeys spend in affiliative behaviors. These data suggest that CRF1 receptor antagonists may not only possess antidepressant and anxiolytic activity, but may be useful in treatment of opiate and benzodiazepine withdrawal.