Estradiol protects against cerebellar damage and motor deficit in ethanol-withdrawn rats

Alcohol. 2002 Feb;26(2):83-93. doi: 10.1016/s0741-8329(01)00199-9.


On the basis of findings obtained from this study, we hypothesize that the female sex steroid 17beta-estradiol (E(2)) protects against cerebellar neuronal damage and behavioral deficit in rats withdrawn from chronic ethanol exposure. Ovariectomized rats implanted with E(2) 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 E(2), 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 E(2). (2) In the absence of E(2), 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 E(2)-treated group. In ethanol withdrawal groups, E(2) 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 E(2) were lower than those in dextrin groups and in the ethanol withdrawal group with E(2) treatment. These findings support the suggestion that E(2) exerts protective effects against withdrawal signs, cerebellar neuronal damage, and motoric impairment in subjects exposed to, and withdrawn from, chronic ethanol exposure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Size / drug effects
  • Cerebellum / drug effects*
  • Cerebellum / pathology
  • Estradiol / blood
  • Estradiol / therapeutic use*
  • Ethanol / adverse effects*
  • Female
  • Motor Skills Disorders / chemically induced
  • Motor Skills Disorders / drug therapy*
  • Motor Skills Disorders / mortality
  • Motor Skills Disorders / pathology
  • Ovariectomy
  • Purkinje Cells / drug effects
  • Purkinje Cells / pathology
  • Rats
  • Rats, Inbred SHR
  • Reaction Time / drug effects
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / mortality
  • Substance Withdrawal Syndrome / pathology


  • Ethanol
  • Estradiol