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Effects of Withdrawal from Chronic Intermittent Ethanol Vapor on the Level and Circadian Periodicity of Running‐Wheel Activity in C57BL/6J and C3H/HeJ Mice
Author(s) -
Logan Ryan W.,
McCulley Walter D.,
Seggio Joseph A.,
Rosenwasser Alan M.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01634.x
Subject(s) - circadian rhythm , wheel running , c57bl/6 , ethanol , period (music) , endocrinology , medicine , psychology , zoology , chemistry , biology , physics , biochemistry , acoustics
Background: Alcohol withdrawal is associated with behavioral and chronobiological disturbances that may persist during protracted abstinence. We previously reported that C57BL/6J (B6) mice show marked but temporary reductions in running‐wheel activity, and normal free‐running circadian rhythms, following a 4‐day chronic intermittent ethanol (CIE) vapor exposure (16 hours of ethanol vapor exposure alternating with 8 hours of withdrawal). In the present experiments, we extend these observations in 2 ways: (i) by examining post‐CIE locomotor activity in C3H/HeJ (C3H) mice, an inbred strain characterized by high sensitivity to ethanol withdrawal, and (ii) by directly comparing the responses of B6 and C3H mice to a longer‐duration CIE protocol.Methods: In Experiment 1, C3H mice were exposed to the same 4‐day CIE protocol used in our previous study with B6 mice (referred to here as the 1‐cycle CIE protocol). In Experiment 2, C3H and B6 mice were exposed to 3 successive 4‐day CIE cycles, each separated by 2 days of withdrawal (the 3‐cycle CIE protocol). Running‐wheel activity was monitored prior to and following CIE, and post‐CIE activity was recorded in constant darkness to allow assessment of free‐running circadian period and phase.Results: C3H mice displayed pronounced reductions in running‐wheel activity that persisted for the duration of the recording period (up to 30 days) following both 1‐cycle (Experiment 1) and 3‐cycle (Experiment 2) CIE protocols. In contrast, B6 mice showed reductions in locomotor activity that persisted for about 1 week following the 3‐cycle CIE protocol, similar to the results of our previous study using a 1‐cycle protocol in this strain. Additionally, C3H mice showed significant shortening of free‐running period following the 3‐cycle, but not the 1‐cycle, CIE protocol, while B6 mice showed normal free‐running rhythms.Conclusions: These results reveal genetic differences in the persistence of ethanol withdrawal‐induced hypo‐locomotion. In addition, chronobiological alterations during extended abstinence may depend on both genetic susceptibility and an extended prior withdrawal history. The present data establish a novel experimental model for long‐term behavioral and circadian disruptions associated with ethanol withdrawal.