title: Lesions of the Edinger-Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption.
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.
authors.affiliation: Department of Behavioural Neuroscience, Oregon Health & Science University and Portland Alcohol Research Center, Portland, OR 97239, USA. ryan.bachtell@UTSouthwestern.edu
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Bachtell
authors.forename: Adam Z
authors.initials: AZ
authors.lastname: Weitemier
authors.forename: Andrey E
authors.initials: AE
authors.lastname: Ryabinin
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature / Q000187:drug effects; D001927:Brain Diseases / Q000503:physiopathology; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004327:Drinking Behavior / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005518:Food Preferences / Q000187:drug effects; D007036:Hypothermia, Induced; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D011803:Quinine; D013395:Sucrose; D013681:Tegmentum Mesencephali / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D054832:Urocortins
chemical_list: D002492:Central Nervous System Depressants; D054832:Urocortins; D000431:Ethanol; D013395:Sucrose; D003346:Corticotropin-Releasing Hormone; D011803:Quinine