Intrahippocampal allopregnanolone decreases voluntary chronic alcohol consumption in non-selected rats

We have recently shown that 0.2 μg of the neurosteroid allopregnanolone (AlloP) administered to the hippocampus induced an anxiolytic-like profile and also reduced alcohol withdrawal symptoms in voluntary and chronic alcohol-drinking rats. The aim of the present work was to study whether the administration of this dose of AlloP could affect alcohol consumption in non-selected rats that have been voluntarily ingesting high doses of alcohol for long periods of time in a limited access procedure. We used a free-choice drinking procedure that involved providing the rats with an alcoholic solution (10% ethanol) at an early age. Alcohol and control rats were assigned randomly to three groups that received an intrahippocampal (dorsal CA1) injection before the period of alcohol consumption after a long history of chronic alcohol intake. The injection groups were AlloP (0.2 μg, 1.26 μM), pregnenolone sulfate (PregS) (5 ng, 24 μM) or vehicle. Blood alcohol concentrations (BAC) were assessed before testing the effects of injections on alcohol consumption. Although AlloP did not eliminate alcohol ingestion, it significantly decreased alcohol consumption. The intrahippocampal administration of PregS, at the dose tested, did not effectively modify alcohol consumption levels. These results indicate that the positive modulation of hippocampal GABAA receptors induced by neurosteroids can be an important neurobiological target for reducing chronic alcohol consumption.