Journal article
Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice
Psychopharmacology (Berlin, Germany), v 233(2), pp 235-242
Jan 2016
PMID: 26449720
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alcohol use disorders are associated with deficits in adaptive behavior. While some behavioral impairments that are associated with alcohol use disorders may predate exposure to drugs of abuse, others may result directly from exposure to drugs of abuse, including alcohol. Identifying a causal role for how alcohol exposure leads to these impairments will enable further investigation of the neurobiological mechanisms by which it acts to dysregulate adaptive behavior.
In the present study, we examined the effects of chronic intermittent ethanol exposure (CIE) on the use of reward-paired cues to guide consummatory behaviors in a mouse model, and further, how manipulations of mGluR2/3 signaling-known to be dysregulated after chronic alcohol exposure-may alter the expression of this behavior.
Adult male C57B/6J mice were trained to self-administer 10 % ethanol and exposed to CIE via vapor inhalation. After CIE exposure, mice were trained in a Pavlovian task wherein a cue (tone) was paired with the delivery of a 10 % sucrose unconditioned stimulus. The use of the reward-paired cue to guide licking behavior was determined across training. The effect of systemic mGluR2/3 manipulation on discrimination between cue-on and cue-off intervals was assessed by administration of the mGluR2/3 agonist LY379268 or the antagonist LY341495 prior to a testing session.
Exposure to CIE resulted in reductions in discrimination between cue-on and cue-off intervals, with CIE-exposed mice exhibiting significantly lower consummatory behavior during reward-paired cues than air controls. In addition, systemic administration of an mGluR2/3 agonist restored the use of reward-paired cues in CIE-exposed animals without impacting behavior in air controls. Conversely, administration of an mGluR2/3 antagonist mimicked the effects of CIE on cue-guided licking behavior, indicating that mGluR2/3 signaling can bidirectionally regulate the ability to use reward-paired cues to guide behavior.
Together, these data suggest that chronic ethanol exposure drives impairments in the ability to use reward-paired cues to adaptively regulate behavior and that mGluR2/3 receptors represent a therapeutic target for restoration of these deficits in behavioral control in the alcoholic.
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Details
- Title
- Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice
- Creators
- Jacqueline M Barker - Medical University of South CarolinaDaniel H Lench - Medical University of South CarolinaL Judson Chandler - Medical University of South Carolina
- Publication Details
- Psychopharmacology (Berlin, Germany), v 233(2), pp 235-242
- Publisher
- Springer Nature
- Number of pages
- 8
- Grant note
- P50 AA010761 / NIAAA NIH HHS U01 AA019967 / NIAAA NIH HHS R01 AA022701 / NIAAA NIH HHS AA023141 / NIAAA NIH HHS TL1 TR001451 / NCATS NIH HHS UL1 TR001450 / NCATS NIH HHS AA010761 / NIAAA NIH HHS AA007474 / NIAAA NIH HHS R01 AA010983 / NIAAA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000367921000006
- Scopus ID
- 2-s2.0-84952880355
- Other Identifier
- 991020100053004721
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InCites Highlights
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- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry