liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
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
Polish Academic Science, Poland .
Polish Academic Science, Poland .
Polish Academic Science, Poland .
Polish Academic Science, Poland .
Show others and affiliations
2013 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 3, 263-270 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Alcohol abuse, dopamine receptor D1, mGluR5, novelty seeking, reward, sensation seeking
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-89509DOI: 10.1016/j.biopsych.2012.07.019ISI: 000313992800011OAI: 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|

Available from: 2013-02-27 Created: 2013-02-26 Last updated: 2013-02-27

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Engblom, David
By organisation
Cell BiologyFaculty of Health Sciences
In the same journal
Biological Psychiatry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 46 hits
ReferencesLink to record
Permanent link

Direct link