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Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice
Journal article   Open access   Peer reviewed

Reversal of alcohol dependence-induced deficits in cue-guided behavior via mGluR2/3 signaling in mice

Jacqueline M Barker, Daniel H Lench and L Judson Chandler
Psychopharmacology (Berlin, Germany), v 233(2), pp 235-242
Jan 2016
DOI: https://doi.org/10.1007/s00213-015-4101-0
PMID: 26449720
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703438View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Adaptation, Psychological - drug effects Alcoholism - psychology Amino Acids - pharmacology Animals Bridged Bicyclo Compounds, Heterocyclic - pharmacology Conditioning, Operant - drug effects Consummatory Behavior - drug effects Cues Excitatory Amino Acid Agonists - pharmacology Excitatory Amino Acid Antagonists - pharmacology Male Mice Mice, Inbred C57BL Psychomotor Performance - drug effects Receptors, AMPA - agonists Receptors, AMPA - antagonists & inhibitors Receptors, AMPA - biosynthesis Reward Self Administration Signal Transduction - drug effects Xanthenes - pharmacology
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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10 citations in Web of Science
10 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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