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Novelty-Seeking Beh...
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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- Rodriguez Parkitna, Jan (författare)
- Polish Academic Science, Poland
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- Sikora, Magdalena (författare)
- Polish Academic Science, Poland
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- Golda, Slawomir (författare)
- Polish Academic Science, Poland
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- Golembiowska, Krystyna (författare)
- Polish Academic Science, Poland
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- Bystrowska, Beata (författare)
- Jagiellonian University, Poland
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- Engblom, David (författare)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Bilbao, Ainhoa (författare)
- Heidelberg University, Germany
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- Przewlocki, Ryszard (författare)
- Polish Academic Science, Poland
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(creator_code:org_t)
- Elsevier, 2013
- 2013
- Engelska.
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 73:3, s. 263-270
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Nyckelord
- Alcohol abuse
- dopamine receptor D1
- mGluR5
- novelty seeking
- reward
- sensation seeking
- MEDICINE
- MEDICIN
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