Sex differences in ethanol-induced hypothermia in ethanol-naïve and ethanol-dependent/withdrawn rats

Alcohol Clin Exp Res. 2009 Jan;33(1):60-9. doi: 10.1111/j.1530-0277.2008.00811.x. Epub 2008 Oct 18.


Background: Human and animal findings indicate that males and females display major differences in risk for and consequences of alcohol abuse and alcoholism. These differences are in large part mediated by sex-specific hormonal environments. Gonadal and adrenal secretory products are known to modulate the neurobehavioral responses of ethanol (EtOH) dependence and withdrawal. However, the effects of these steroids on physiological adaptations, such as thermoregulation, are less well established. To study the role of sex-related hormones in mediating sex differences in the hypothermic response to acute challenge with EtOH, we compared the EtOH-induced hypothermic responses of EtOH-naïve male and female rats and EtOH-dependent (on the third day of withdrawal) male and female rats before (intact) and after depletion of all gonadal and adrenal steroids by gonadectomy (GDX) with or without adrenalectomy (ADX).

Methods: Intact and GDX male and female rats, with or without ADX, were fed an EtOH-containing liquid diet for 15 days while control (EtOH-naïve) rats were pairfed the isocaloric liquid diet without EtOH or fed normal rat chow and water. On the third day of withdrawal from the EtOH diet we tested the hypothermic response to EtOH challenge (1.5 g/kg BWt, ip). Blood alcohol content (BAC) and corticosterone (CORT) content were analyzed in a separate series of intact and GDX males and females with and without ADX in response to the EtOH challenge.

Results: Ethanol-induced hypothermia was significantly greater and its duration significantly longer in intact males than females when subjects were EtOH-naïve. EtOH-induced hypothermia was significantly greater in intact females than males by the third day of withdrawal from EtOH dependence. GDX in males significantly shortened the duration of the hypothermic response and tended to blunt EtOH-induced hypothermia while response duration was significantly extended by GDX in females that tended to enhance EtOH-hypothermia. EtOH-induced hypothermia was significantly enhanced and its duration significantly lengthened by combined GDX and ADX in EtOH-naïve and -withdrawn males and by combined GDX and ADX in EtOH-naïve but not EtOH-withdrawn females. These differential EtOH-induced hypothermic responses did not appear to be caused by differences in EtOH handling among the groups. The absence of adrenal activation by EtOH in the GDX-ADX males and females contributes to their enhanced EtOH-induced hypothermic responses.

Conclusions: These results implicate the direct and indirect effects of removal of gonadal and adrenal secretory products as mediators of the thermoregulatory actions of EtOH.

Publication types

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

MeSH terms

  • Alcoholism / blood
  • Alcoholism / physiopathology*
  • Animals
  • Ethanol / administration & dosage*
  • Female
  • Hypothermia / blood
  • Hypothermia / chemically induced*
  • Hypothermia / physiopathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sex Characteristics*
  • Substance Withdrawal Syndrome / blood
  • Substance Withdrawal Syndrome / physiopathology*


  • Ethanol