Chronic intermittent ethanol exposure during adolescence reduces the effect of ethanol challenge on hippocampal allopregnanolone levels and Morris water maze task performance

Abstract

Chronic intermittent ethanol exposure (CIEE) in adolescent rats has been shown to produce long-lasting hypnotic, metabolic, and functional tolerance. Recently, it has been hypothesized that allopregnanolone mediates some effects of ethanol, including ethanol-induced impairments in the performance of the Morris Water Maze Task (MWMT). The current studies explore the relationship between cortical and hippocampal allopregnanolone levels and ethanol-induced impairments in the MWMT following CIEE treatment in adolescent rats. Adolescent rats were administered 5.0 g/kg ethanol or saline every 48 h for a 20-day period beginning on postnatal day (P) 30. Training in the spatial version of the MWMT occurred on nontreatment days. Following completion of CIEE treatment and training, MWMT performance was tested 30 min after ethanol (2.0 g/kg) or saline challenge on P 50 and P 62. A separate group of rats were CIEE treated and received an ethanol (2.0 g/kg) or saline challenge on P 50 or 62, and were used for hippocampal and cortical allopregnanolone determination. CIEE during adolescence produced tolerance to both ethanol-induced impairments in the MWMT and ethanol-induced allopregnanolone levels in the hippocampus on P 50. However, when animals were tested at P 62, the reduction in ethanol-induced MWMT impairments found in CIEE rats was reversed and allopregnanolone levels from both saline or ethanol challenge were increased above levels found in control animals. Taken together, these results suggest that CIEE during adolescence produces tolerance to ethanol-induced impairments in MWMT and corresponding changes in ethanol-induced allopregnanolone levels in the hippocampus. Furthermore, cognitive tolerance is reversible and time dependent, but the reversal of cognitive tolerance is not correlated with normalization of hippocampal allopregnanolone levels.