ANTIDEPRESSANT-LIKE EFFECTS OF CP-154,526, A SELECTIVE CRF(1) RECEPTOR ANTAGONIST

The effects of CP-154,526 l-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-a mine), a selective corticotropin releasing factor (CRF,) receptor anta gonist, were examined in the learned helplessness procedure, a putativ e model of depression with documented sensitivity to diverse classes o f antidepressant drugs. Rats were exposed to a series of inescapable f oot shocks on three consecutive days and tested in a shock-escape proc edure on the fourth day. Animals exposed to 'helplessness' training pe rformed poorly in the shock-escape test compared with control animals not receiving inescapable shocks. CP-154,526 (10-32 mg/kg, intraperito neally) dose-dependently reversed the escape deficit when administered 60 min prior to the test session, but had no effect on the performanc e of control rats not receiving prior exposure to inescapable stress. In comparison, the tricyclic antidepressant imipramine (17.8 mg/kg) re versed the escape deficit after repeated, but not acute, administratio n. These data support evidence implicating stress systems in the patho physiology of depression, and suggest potential efficacy of small-mole cule CRF receptor antagonists in the treatment of affective disorders. (C) 1997 Elsevier Science B.V.