Synthetic epoxy-pregnan steroids: Effects on anxiety behavior in rats

COIRINI, H.; GHINI, A.A.; REY, M.

JOURNAL OF STEROIDS & HORMONAL SCIENCE

OMICS International

Año: 2016 vol. 7 p. 167 - 175

Neurosteroids like 3a-OH-5a-pregnan-20-one(allopregnanolone)and 3a-OH-5b-pregnan-20-one(pregnanolone) modulate the g-aminobutyric acid-A(GABAA)receptor function and produce several effects that can beconsidered for therapeuticalpruposes like antidepressant and anxiolyticts, in asimilar way tobenzodiazepines. However, their rapid metabolism is a greatdisadvantage formedicinal treatments consideration. Synthetic steroid analogueswith morebioavailability and stability arise like a solution to overcometheselimitations. In previous studies, we evaluated the performance of asyntheticsteroid group (Epoxies, similar toallopregnanolone andpregnanolone) throughout different assays in rat cerebralcortex andhippocampus, including neuroprotection and GABAA receptormodulationobtaining promising results. Taking into account the anxiolyticeffect ofallopregnanolone and pregnanolone, in this work we evaluated theeffect of anintracranial administration (in dorsal hippocampus) of twosynthetic steroids, Epoxy1 and Epoxy 2, in an anxiety animal model toprovide knowledge aboutthe possible invivo effects of these steroids. Allopregnanolone andpregnanolone producedincreases in vertical and horizontal exploration behaviors, interpreted asanxiolytic-like effects. However, the two Epoxiescapableto modulate GABAA receptor binding have no effect on anxietyat thedose evaluated. These features make them suitable for othertherapeuticalpurposes where the anxiogenic behaviors are not involved.