Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress

Evaluation of the effect of doxasozin and zonisamide on voluntary ethanol intake in mice that experienced chronic intermittent ethanol exposure and stress

The comorbidity between alcohol use disorder and post-traumatic stress disorder represents a serious health care burden with few effective treatment options. The current study was designed to evaluate the effect of an alpha 1 receptor antagonist (doxazosin) and a novel anticonvulsant (zonisamide) in...

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Bibliographic Details
Published in:Alcohol (Fayetteville, N.Y.) Vol. 89; pp. 37 - 42
Main Authors: Lopez, Marcelo F., Reasons, Sarah E., Carper, Benjamin A., Nolen, Tracy L., Williams, Rick L., Becker, Howard C.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-12-2020
Elsevier Limited
Subjects:
Alcohol Drinking
Alcohol use
Alcoholism
Animals
Anticonvulsants
Clinical trials
Cocaine
Comorbidity
Cytotoxicity
Doxazosin
Doxazosin - pharmacology
Drinking behavior
Drug dependence
Drug dosages
Ethanol
Ethanol - administration & dosage
Ethanol dependence
Female
Females
Laboratory animals
Lymphocytes T
Male
Males
Mice
Mice, Inbred C57BL
Mouse
Post traumatic stress disorder
Stress
Stress, Physiological
Zonisamide
Zonisamide - pharmacology
Doxazosin
Mouse
Stress
Ethanol dependence
Zonisamide
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Summary:The comorbidity between alcohol use disorder and post-traumatic stress disorder represents a serious health care burden with few effective treatment options. The current study was designed to evaluate the effect of an alpha 1 receptor antagonist (doxazosin) and a novel anticonvulsant (zonisamide) in a model of alcohol (ethanol) dependence and stress exposure. The main dependent variable was voluntary ethanol intake in mice that experienced chronic intermittent ethanol (CIE) exposure and forced swim stress (FSS) alone, and in combination. Adult male and female C57BL/6J mice had access to a single bottle of 15% (v/v) ethanol for 1-hr in the home cage, 3-hr into the dark phase of the light/dark cycle. Once stable ethanol intake was established (~4 weeks), mice were separated into four groups (CTL, CIE, FSS, CIE + FSS). Mice in the FSS condition received 10-min FSS exposure 4-hr prior to drinking sessions (remaining mice were not disturbed). During baseline and the first two test cycles, all mice received vehicle (saline) injections (IP) 30-min before ethanol access. As previously observed, FSS increased ethanol drinking in dependent (CIE-exposed) mice but not in nondependent control (CTL) mice. In the following test cycles mice were evaluated for ethanol intake after administration of doxazosin, zonisamide or their combination. Results indicated that the three doses of doxazosin evaluated significantly reduced voluntary ethanol intake in all mice. Zonisamide had a more modest effect and may require a more prolonged treatment regime. The combined administration of both compounds was not more effective than each drug alone. This study suggests that doxazosin is reliable at reducing voluntary ethanol intake in mice independently of their history of ethanol dependence and stress exposure. •CIE exposure leads to high ethanol intake in mice that experienced stress.•Doxasozin reduced ethanol intake independently of CIE exposure or stress.•Zonisamide had a more limited effect reducing voluntary ethanol intake.•The combination of these drugs was not more effective at reducing ethanol intake.
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ISSN:0741-8329
1873-6823
DOI:10.1016/j.alcohol.2020.07.005