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

Abstract

Neurosteroids like 3α-OH-5α-pregnan-20-one (allopregnanolone) and 3α-OH-5β-pregnan-20-one (pregnanolone) modulate the γ-aminobutyric acid-A (GABAA) receptor function and produce several effects that can be considered for therapeutical pruposes like antidepressant and anxiolyticts, in a similar way to benzodiazepines. However, their rapid metabolism is a great disadvantage for medicinal treatments consideration. Synthetic steroid analogues with more bioavailability and stability arise like a solution to overcome these limitations. In previous studies, we evaluated the performance of a synthetic steroid group (Epoxies, similar to allopregnanolone and pregnanolone) throughout different assays in rat cerebral cortex and hippocampus, including neuroprotection and GABAA receptor modulation obtaining promising results. Taking into account the anxiolytic effect of allopregnanolone and pregnanolone, in this work we evaluated the effect of an intracranial administration (in dorsal hippocampus) of two synthetic steroids, Epoxy 1 and Epoxy 2, in an anxiety animal model to provide knowledge about the possible in vivo effects of these steroids. Allopregnanolone and pregnanolone produced increases in vertical and horizontal exploration behaviors, interpreted as anxiolytic-like effects. However, the two Epoxies capable to modulate GABAA receptor binding have no effect on anxiety at the dose evaluated. These features make them suitable for other therapeutical purposes where the anxiogenic behaviors are not involved.