Abstracts

Androstenol (5[alpha]-androst-16-en-3[alpha]-ol) is a volatile steroid compound belonging to the group of odorous 16-androstenes. It was first isolated from boar saliva, but it is also found in human plasma. Androstenol is structurally similar to endogenous A-ring reduced steroids that act as positive modulators of GABA-A receptors, i.e. neurosteroids. Thus, we have hypothesized that androstenol may have electrophysiological and behavioral traits characteristic for neurosteroids. The influence of androstenol on GABA-A receptors currents under voltage clamp conditions in mouse cerebellar granule cell cultures, mouse brain slices and HEK cells expressing human GABA-A [sub][/sub]receptor subunits has been assessed. Additionally, the effect of androstenol on 4-AP induced epileptiform activity in rat hippocampal slices was studied. Assessment of anticonvulsant, anxiolytic and antidepressant effects of androstenol in 6 Hz, PTZ, open field and forced swim models, respectively. We have found that androstenol potentiates GABA-evoked currents in HEK cells as well as in cerebellar cultures and slices. Androstenol inhibited epileptiform activity induced by 4-AP in rat brain slices and had strong anticonvulsant effects against PTZ- and 6 Hz-induced seizures in mice. In addition, we have found that androstenol has anxiolytic and antidepressant effects in animal models. These results for the first time demonstrate that androstenol acts as a positive modulator of GABA-A receptors and has behavioral properties compatible with this physiological action. Androstenol could be an endogenous modulator of GABA-A receptors, and it might be useful in epilepsy treatment. (Supported by NINDS/NIH.)