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

• Verfasst von: Rodriguez-Parkitna, Jan [VerfasserIn]
• Verfasst von: Sikora, Magdalena [VerfasserIn]
• Verfasst von: Gołda, Sławomir [VerfasserIn]
• Verfasst von: Gołembiowska, Krystyna [VerfasserIn]
• Verfasst von: Bystrowska, Beata [VerfasserIn]
• Verfasst von: Engblom, David [VerfasserIn]
• Verfasst von: Bilbao, Ainhoa [VerfasserIn]
• Verfasst von: Przewlocki, Ryszard [VerfasserIn]
• Titel: 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
• Verf.angabe: Jan Rodriguez Parkitna, Magdalena Sikora, Sławomir Gołda, Krystyna Gołembiowska, Beata Bystrowska, David Engblom, Ainhoa Bilbao, and Ryszard Przewlocki
• Jahr: 2013
• Umfang: 8 S.
• Fussnoten: Gesehen am 31.03.2022
• Titel Quelle: Enthalten in: Biological psychiatry
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1985
• Jahr Quelle: 2013
• Band/Heft Quelle: 73(2013), 3, Seite 263-270
• ISSN Quelle: 1873-2402
• DOI: doi:10.1016/j.biopsych.2012.07.019
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alcohol abuse
• Sach-SW: dopamine receptor D1
• Sach-SW: mGluR5
• Sach-SW: novelty seeking
• Sach-SW: reward
• Sach-SW: sensation seeking
• K10plus-PPN: 1797154400

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 (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.