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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

Authors

  • Ryan W. Logan,

    1. From the Graduate School of Biomedical Sciences (RWL, AMR), University of Maine, Orono, Maine; Department of Psychology (RWL, WDM, AMR), University of Maine, Orono, Maine; and School of Biology and Ecology (JAS, AMR), University of Maine, Orono, Maine.
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  • Walter D. McCulley III,

    1. From the Graduate School of Biomedical Sciences (RWL, AMR), University of Maine, Orono, Maine; Department of Psychology (RWL, WDM, AMR), University of Maine, Orono, Maine; and School of Biology and Ecology (JAS, AMR), University of Maine, Orono, Maine.
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  • Joseph A. Seggio,

    1. From the Graduate School of Biomedical Sciences (RWL, AMR), University of Maine, Orono, Maine; Department of Psychology (RWL, WDM, AMR), University of Maine, Orono, Maine; and School of Biology and Ecology (JAS, AMR), University of Maine, Orono, Maine.
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  • Alan M. Rosenwasser

    1. From the Graduate School of Biomedical Sciences (RWL, AMR), University of Maine, Orono, Maine; Department of Psychology (RWL, WDM, AMR), University of Maine, Orono, Maine; and School of Biology and Ecology (JAS, AMR), University of Maine, Orono, Maine.
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  •  Present address: Ryan W. Logan, Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey.

  •  Present address: Joseph A. Seggio, Department of Biology, Bridgewater State University, Bridgewater, Massachusetts.

Reprint requests: Alan M. Rosenwasser, PhD, Department of Psychology, University of Maine, Orono, ME 04469-5742; Tel.: 207-581-2035; Fax: 207-581-6128; E-mail: alanr@maine.edu

Abstract

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.

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