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.
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.
Graduate School of Biomedical Sciences, University of Maine, Orono, Maine 04469-5742, USA.
Ryan W
RW
Logan
Walter D
WD
McCulley
Joseph A
JA
Seggio
Alan M
AM
Rosenwasser
D000280:Administration, Inhalation; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H / Q000502:physiology*; D008810:Mice, Inbred C57BL / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D000431:Ethanol