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
2013 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 3, 263-270 p.Article in journal (Refereed) Published
Background: Novel experiences activate the brains 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. less thanbrgreater than less thanbrgreater thanMethods: 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. less thanbrgreater than less thanbrgreater thanResults: 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. less thanbrgreater than less thanbrgreater thanConclusions: These data identify mGluR5 receptors on D1-expressing neurons as a common molecular substrate of novelty-seeking behaviors and behaviors associated with alcohol abuse.
Place, publisher, year, edition, pages
Elsevier , 2013. Vol. 73, no 3, 263-270 p.
Alcohol abuse, dopamine receptor D1, mGluR5, novelty seeking, reward, sensation seeking
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-89509DOI: 10.1016/j.biopsych.2012.07.019ISI: 000313992800011OAI: oai:DiVA.org:liu-89509DiVA: diva2:608382
Funding Agencies|Polish Ministry of Science and Higher Education|N405 143238|Institute of Pharmacology of Polish Academy of Sciences||Department of Toxicology of Faculty of Pharmacy of Jagiellonian University Collegium Medicum||European Research Council||Swedish Research Council||German Bundesministerium fur Bildung und Forschung (National Genome Research Network Plus)|FKZ: 01GS08152|2013-02-272013-02-262013-02-27