Neurosteroid consumption has anxiolytic effects in mice

Abstract

The neurosteroids allopregnanolone (ALLOP) and pregnanolone (PREG), like ethanol, potentiate γ-aminobutyric acid A receptor function. PREG-hemisuccinate (PREG-HS) is a negative modulator of N-methyl- d-aspartate (NMDA) receptors. Because C57BL/6J (B6) and DBA/2J (D2) mice differ in ethanol preference, voluntary consumption of ALLOP and PREG-HS (50 μg/ml solution) versus tap water was measured in B6 and D2 mice for a minimum of 8 days. Mice were acclimated to a reverse light–dark cycle prior to the initiation of experiments. In the first study, both B6 and D2 mice exhibited preference for the PREG-HS solution. In the second study, neither strain exhibited significant preference for the ALLOP solution versus water. However, the ALLOP-consuming B6 and D2 mice exhibited significant anxiolysis when they were tested on the elevated plus maze following 8 days of ALLOP consumption, compared to separate animals that consumed only water. A subsequent study determined that systemic administration of PREG-HS had significant anxiolytic effects in both B6 and D2 mice, when assessed on the elevated plus maze. Plasma ALLOP levels in the steroid-consuming mice from both studies were significantly increased versus basal levels only in the D2 strain. While the pattern of steroid intake or strain differences in steroid conversion may have influenced the differential change in plasma ALLOP levels, it is noteworthy that both strains consumed doses of ALLOP, and presumably doses of PREG-HS, that were anxiolytic.