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 (2012)

COMMENTS: Complex study, but two points are clear

  1. Novelty activates reward circuit
  2. It does this by activating the same mechanisms as alcohol binging (which will probbaly apply to all addictive substances)

Biol Psychiatry. 2012 Aug 16. 


Department of Molecular Neuropharmacology, Institute of Pharmacology of the Polish Academy of Sciences, Krakow, Poland.



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.


Mice harboring a transgene expressing microRNA hairpins against mGluR5 messenger RNA under the control of the D1 dopamine receptor gene promoter (mGluR5(KD-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.


mGluR5(KD-D1) mice showed no behavioral deficits and exhibited normal anxiety-like behaviors and learning abilities. However, mGluR5(KD-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 mGluR5(KD-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.


These data identify mGluR5 receptors on D1-expressing neurons as a common molecular substrate of novelty-seeking behaviors and behaviors associated with alcohol abuse.

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

[PubMed – as supplied by publisher]