Effect of ORG 34116, a corticosteroid receptor antagonist, on hippocampal Ca2+ currents

ORG 34116, a substituted 11,21-bisarylsteroid compound, binds selectively and with high affinity to human and rat glucocorticoid receptors. At the level of the hypothalamus it attenuates the negative feedback action of corticosterone, suggesting that it acts as an antagonist. In the present study we examined the effect of in vitro and in vivo administered ORG 34116 on cell properties of higher brain areas, i.e. on Ca2+ current characteristics of CAI hippocampal neurons recorded with whole cell techniques in hippocampal slices. We observed that in vitro applied ORG 34116 antagonized corticosterone induced effects on Ca2+ currents. Data observed after in vivo application of ORG 34116 corroborate these findings. The results furthermore suggest that pretreatment with the glucocorticoid receptor antagonist ORG 34116 also prevents the development of mineralocorticoid receptor mediated effects on Ca2+ currents. 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 disorders.