Chronic exposure to ethanol during adolescence has also revealed long-lasting changes in hippocampal function and GABAergic neuroactive steroids. For example, CIE exposure to high dose ethanol during adolescence does not impair spatial learning during the exposure (Silvers et al. 2003a) but does produce cognitive tolerance to ethanol’s memory impairing effects when animals are tested as young adults (Silvers et al. 2003b, 2006). However, the cognitive tolerance is not permanent (Silvers et al. 2006) and may in fact lead to sensitization of ethanol’s effect on memory following a long delay (White et al. 2000). Mirroring the cognitive tolerance, CIE exposure during adolescence blunts ethanol-induced inhibition of hippocampal pyramidal neurons, and this effect lasts into young adulthood (Tokunaga et al. 2006). Furthermore, chronic intermittent ethanol during adolescence also reduces hippocampal 3α,5α-THP levels in response to an ethanol challenge (Silvers et al. 2006) and this reduced neuroactive steroid response directly mirrors the reduced cognitive and neurophysiological effect following ethanol challenge. Therefore, it is likely that the prolonged cognitive and neurophysiological tolerance found following chronic ethanol exposure during adolescence is due to GABAergic mechanisms
