EFFECT OF ORG-34116, A CORTICOSTEROID RECEPTOR ANTAGONIST, ON HIPPOCAMPAL CA2(+) CURRENTS

ORG 34116, a substituted 11,21-bisarylsteroid compound, binds selectiv ely and with high affinity to human and rat glucocorticoid receptors. At the level of the hypothalamus it attenuates the negative feedback a ction of corticosterone, suggesting that it acts as an antagonist. In the present study we examined the effect of in vitro and in vivo admin istered ORG 34116 on cell properties of higher brain areas, i.e. on Ca 2+ current characteristics of CA1 hippocampal neurons recorded with wh ole cell techniques in hippocampal slices. We observed that in vitro a pplied ORG 34116 antagonized corticosterone induced effects on Ca2+ cu rrents. Data observed after in vivo application of ORG 34116 corrobora te these findings. The results furthermore suggest that pretreatment w ith the glucocorticoid receptor antagonist ORG 34116 also prevents the development of mineralocorticoid receptor mediated effects on Ca2+ cu rrents. If ORG 34116 should indeed prove to be a corticosterone rather than glucocorticoid receptor selective antagonist, this drug may turn out to be an important tool in the treatment of stress-related disord ers. (C) 1997 Elsevier Science B.V.