Lesions of the Edinger-Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption

Eur J Neurosci. 2004 Sep;20(6):1613-23. doi: 10.1111/j.1460-9568.2004.03594.x.

Abstract

The Edinger-Westphal nucleus (EW) is a brain region that has recently been implicated as an important novel neural target for ethanol. Thus, the EW is the only brain region consistently showing elevated c-Fos expression following both voluntary and involuntary ethanol administration. Ethanol-induced c-Fos expression in the EW has been shown to occur in urocortin I-positive neurons. Moreover, previous reports using several genetic models have demonstrated that differences in the EW urocortin I system are correlated with ethanol-mediated behaviours such as ethanol-induced hypothermia and ethanol consumption. The aim of this study was to confirm these relationships using a more direct strategy. Thus, ethanol responses were measured following electrolytic lesions of the EW in male C57BL/6J mice. Both EW-lesioned and sham-operated animals were tested for several ethanol sensitivity measures and ethanol consumption in a two-bottle choice test. The results show that lesions of the EW significantly disrupted ethanol-induced hypothermia, while having no effect on pupillary dilation, locomotor activity or ethanol-induced sedation. In addition, EW-lesioned animals showed significantly lower ethanol preference and total ethanol dose consumed in the two-bottle choice test. EW-lesioned animals also consumed less sucrose than sham-operated animals, but did not have altered preferences for sucrose or quinine in a two-bottle choice test. These data support previously observed genetic correlations between EW urocortin I expression and both ethanol-induced hypothermia and ethanol consumption. Taken together, the findings suggest that the EW may function as a sensor for ethanol, which can influence ethanol consumption and preference.

Publication types

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

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Animals
  • Behavior, Animal
  • Body Temperature / drug effects
  • Brain Diseases / physiopathology
  • Cell Count
  • Central Nervous System Depressants / metabolism*
  • Corticotropin-Releasing Hormone / metabolism
  • Drinking Behavior / drug effects
  • Ethanol / metabolism*
  • Ethanol / pharmacology
  • Food Preferences / drug effects
  • Hypothermia, Induced*
  • Immunohistochemistry / methods
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Pupil / drug effects
  • Quinine
  • Sucrose
  • Tegmentum Mesencephali / injuries
  • Tegmentum Mesencephali / pathology
  • Tegmentum Mesencephali / physiopathology*
  • Urocortins

Substances

  • Central Nervous System Depressants
  • Urocortins
  • Ethanol
  • Sucrose
  • Corticotropin-Releasing Hormone
  • Quinine