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Biol Psychiatry. 2013 Feb 1;73(3):263-70. doi: 10.1016/j.biopsych.2012.07.019. Epub 2012 Aug 16.

Novelty-seeking behaviors and the escalation of alcohol drinking after abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing dopamine d1 receptors.

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  • 1Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Krakow, Poland.

Abstract

BACKGROUND:

Novel experiences activate the brain's reward system in a manner similar to drugs of abuse, and high levels of novelty-seeking and sensation-seeking behavior have been associated with increased susceptibility to alcohol and drug abuse. Here, we show that metabotropic glutamate receptor 5 (mGluR5) signaling on dopaminoceptive neurons is necessary for both novelty-seeking behavior and the abstinence-induced escalation of alcohol drinking.

METHODS:

Mice harboring a transgene expressing microRNA hairpins against mGluR5 messenger RNA under the control of the D1 dopamine receptor gene promoter (mGluR5(KD-D1)) were tested in a battery of behavioral tests measuring learning abilities, anxiety levels, reactions to novelty, operant sensation seeking, and alcohol sensitivity. In addition, we have developed a method to assess long-term patterns of alcohol drinking in mice housed in groups using the IntelliCage system.

RESULTS:

mGluR5(KD-D1) mice showed no behavioral deficits and exhibited normal anxiety-like behaviors and learning abilities. However, mGluR5(KD-D1) animals showed reduced locomotor activity when placed in a novel environment, and exhibited decreased interaction with a novel object. Moreover, unlike control animals, mutant mice did not perform instrumental responses under the operant sensation-seeking paradigm, although they learned to respond for food normally. When mGluR5(KD-D1) mice were provided access to alcohol, they showed similar patterns of consumption as wild-type animals. However, mutant mice did not escalate their alcohol consumption after a period of forced abstinence, but control mice almost doubled their intake.

CONCLUSIONS:

These data identify mGluR5 receptors on D1-expressing neurons as a common molecular substrate of novelty-seeking behaviors and behaviors associated with alcohol abuse.

PMID:
22902169
DOI:
10.1016/j.biopsych.2012.07.019
[PubMed - indexed for MEDLINE]
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