Estradiol protects against cerebellar damage and motor deficit in ethanol-withdrawn rats

On the basis of findings obtained from this study, we hypothesize that the female sex steroid 17β-estradiol (E₂) protects against cerebellar neuronal damage and behavioral deficit in rats withdrawn from chronic ethanol exposure. Ovariectomized rats implanted with E₂ or an oil pellet received liquid ethanol (7.5% [wt./vol.]) or dextrin diet for 5 weeks, followed by 2 weeks of ethanol withdrawal. On termination of diet administration, rats were tested for both overt withdrawal signs and latency (seconds) to fall from an accelerating rotarod in six consecutive sessions (the longer the latency, the better the performance). The initial latency was measured separately to assess motoric capacity before learning occurred. Rats were then killed, and cerebella were prepared for accessing of Purkinje cell damage. The study revealed three specific findings. (1) In the absence of E₂, the ethanol withdrawal group showed higher total ethanol withdrawal sign scores than those for the dextrin group, whereas the score for the ethanol withdrawal group was lower in the presence of E₂. (2) In the absence of E₂, the ethanol withdrawal group showed shorter rotarod latency than that for the dextrin group, whereas the latency for the ethanol withdrawal group increased in the E₂-treated group. In ethanol withdrawal groups, E₂ treatment also resulted in a longer latency than that observed with oil treatment in the initial session and in subsequent sessions. (3) Purkinje cell numbers in the ethanol withdrawal group without E₂ were lower than those in dextrin groups and in the ethanol withdrawal group with E₂ treatment. These findings support the suggestion that E₂ exerts protective effects against withdrawal signs, cerebellar neuronal damage, and motoric impairment in subjects exposed to, and withdrawn from, chronic ethanol exposure.