The lack of conditioned place preference, but unaltered stimulatory and ataxic effects of alcohol in mGluR3-KO mice

J Psychopharmacol. 2019 Jul;33(7):855-864. doi: 10.1177/0269881119844178. Epub 2019 May 9.


Background: Alcohol use associates with environmental cues that can later reinstate drinking patterns without any alcohol exposure. Alcohol-induced reward, when combined with contextual signals of various sensory modalities in the central synapses of mesolimbic reward circuitries, can lead to the formation of conditioned responses.

Aims: As the activation of glutamatergic synapses is pivotal in such processes, we aimed to investigate whether the metabotropic glutamate receptor subtype 3 plays a role in alcohol-induced behaviours including place preference.

Methods: The metabotropic glutamate receptor subtype 3 knockout (mGluR3-KO) mouse line was used to study alcohol-induced place preference, locomotor activating and ataxic effects, limited access alcohol drinking, and preference for sucrose and saccharin.

Results: Alcohol-induced horizontal locomotor stimulation and reduced rearing behaviour remained unchanged in the mGluR3-KO mice. However, alcohol-induced place conditioning in an unbiased paradigm setup was lacking in the mGluR3-KO mice, but clearly present in wildtype mice. Locomotor activity was not different between the mGluR3-KO and wildtype mice during the acquisition and expression trials. Alcohol consumption, studied through the 'drinking in the dark' model, remained unchanged in the mGluR3-KO mice, although low consumption in both wildtype and knockout mice hampers interpretation. The mGluR3-KO mice also showed normal sucrose and saccharin preference.

Conclusions: These studies indicate a role for metabotropic glutamate receptor subtype 3 in the conditioned contextual alcohol responses, but not in stimulatory, and ataxic alcohol effects.

Keywords: Ethanol; conditioned place preference; metabotropic glutamate receptor 3; metabotropic glutamate receptor subtype 3 knockout; reward.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / psychology*
  • Animals
  • Conditioning, Psychological / drug effects*
  • Cues
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Locomotion / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Metabotropic Glutamate / genetics*
  • Reward


  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 3
  • Ethanol