TY - JOUR
T1 - Environmental stressors influence limited-access ethanol consumption by C57BL/6J mice in a sex-dependent manner
AU - Cozzoli, Debra K.
AU - Tanchuck-Nipper, Michelle A.
AU - Kaufman, Moriah N.
AU - Horowitz, Chloe B.
AU - Finn, Deborah A.
N1 - Funding Information:
Funding for these studies was provided by a grant from the Department of Veterans Affairs (BX001070, DAF). Additionally, this material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center (DAF). DKC was supported by a training grant (NIAAA, T32 AA007468) as well as RO1 AA016981 (NIAAA, awarded to DAF). CBH was supported by the VA College Summer Student Fellowship Program. The C57BL/6J mice were supplied from a breeding colony that was maintained by the Portland Alcohol Research Center (NIAAA, P60 AA10760 awarded to Dr. John C. Crabbe). We also thank two anonymous reviewers for their careful evaluation of this manuscript and their helpful suggestions.
Publisher Copyright:
© 2014 .
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Exposure to stress contributes to ethanol consumption in humans, but it produces inconsistent effects on ethanol drinking in rodent models. Therefore, the present study examined the influence of different stressors (restraint, tail suspension, predator odor, foot shock, and tail pinch) on 2-h access to water and 10% ethanol by male and female C57BL/6J mice and determined whether there were sex-dependent differences in response to stress. Plasma corticosterone (CORT) and allopregnanolone (ALLO) were assessed as indexes of hypothalamic-pituitary-adrenal axis activity and of endogenous neurosteroid levels, respectively, following restraint, tail suspension, and predator odor. These stressors increased plasma CORT and ALLO levels, and produced a greater increase in CORT and ALLO levels in females versus males. Ethanol intake was decreased following restraint, tail suspension, foot shock, and tail pinch in both sexes, with stressor-related differences in the duration of the suppression. Predator odor significantly increased ethanol intake on the following two days in females and on the second day after stress in males. Notably, there was a significant positive correlation between CORT levels immediately after predator odor stress and ethanol intake on the following day. In summary, the type of stressor influenced ethanol consumption, with subtle sex differences in the magnitude and persistence of the effect. These findings are the first to demonstrate that a single, acute exposure to restraint, tail suspension, and predator odor stress increased plasma CORT and ALLO levels in animals with a history of ethanol consumption and that female mice were more responsive than males to the ability of stress to increase CORT and ALLO levels as well as to increase ethanol intake following predator odor stress. Because predator odor stress is a model of post-traumatic stress disorder (PTSD), the present sex differences have important implications for preclinical studies modeling the comorbidity of PTSD and alcohol use disorders.
AB - Exposure to stress contributes to ethanol consumption in humans, but it produces inconsistent effects on ethanol drinking in rodent models. Therefore, the present study examined the influence of different stressors (restraint, tail suspension, predator odor, foot shock, and tail pinch) on 2-h access to water and 10% ethanol by male and female C57BL/6J mice and determined whether there were sex-dependent differences in response to stress. Plasma corticosterone (CORT) and allopregnanolone (ALLO) were assessed as indexes of hypothalamic-pituitary-adrenal axis activity and of endogenous neurosteroid levels, respectively, following restraint, tail suspension, and predator odor. These stressors increased plasma CORT and ALLO levels, and produced a greater increase in CORT and ALLO levels in females versus males. Ethanol intake was decreased following restraint, tail suspension, foot shock, and tail pinch in both sexes, with stressor-related differences in the duration of the suppression. Predator odor significantly increased ethanol intake on the following two days in females and on the second day after stress in males. Notably, there was a significant positive correlation between CORT levels immediately after predator odor stress and ethanol intake on the following day. In summary, the type of stressor influenced ethanol consumption, with subtle sex differences in the magnitude and persistence of the effect. These findings are the first to demonstrate that a single, acute exposure to restraint, tail suspension, and predator odor stress increased plasma CORT and ALLO levels in animals with a history of ethanol consumption and that female mice were more responsive than males to the ability of stress to increase CORT and ALLO levels as well as to increase ethanol intake following predator odor stress. Because predator odor stress is a model of post-traumatic stress disorder (PTSD), the present sex differences have important implications for preclinical studies modeling the comorbidity of PTSD and alcohol use disorders.
KW - Allopregnanolone
KW - Corticosterone
KW - Environmental stress
KW - Foot shock
KW - Predator odor
KW - Tail pinch
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U2 - 10.1016/j.alcohol.2014.07.015
DO - 10.1016/j.alcohol.2014.07.015
M3 - Article
C2 - 25459519
AN - SCOPUS:84922814978
VL - 48
SP - 741
EP - 754
JO - Alcohol
JF - Alcohol
SN - 0741-8329
IS - 8
ER -