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

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 rece...

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Hauptverfasser: Rodriguez-Parkitna, Jan (VerfasserIn) , Sikora, Magdalena (VerfasserIn) , Gołda, Sławomir (VerfasserIn) , Gołembiowska, Krystyna (VerfasserIn) , Bystrowska, Beata (VerfasserIn) , Engblom, David (VerfasserIn) , Bilbao, Ainhoa (VerfasserIn) , Przewlocki, Ryszard (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2013
In: Biological psychiatry
Year: 2013, Jahrgang: 73, Heft: 3, Pages: 263-270
ISSN:1873-2402
DOI:10.1016/j.biopsych.2012.07.019
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.biopsych.2012.07.019
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006322312006312
Volltext
Verfasserangaben:Jan Rodriguez Parkitna, Magdalena Sikora, Sławomir Gołda, Krystyna Gołembiowska, Beata Bystrowska, David Engblom, Ainhoa Bilbao, and Ryszard Przewlocki

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520 |a 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 (mGluR5KD-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 - mGluR5KD-D1 mice showed no behavioral deficits and exhibited normal anxiety-like behaviors and learning abilities. However, mGluR5KD-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 mGluR5KD-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. 
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