Pharmacological modulation of mGluR7 with AMN082 and MMPIP exerts specific influences on alcohol consumption and preference in rats

Addict Biol. 2012 Mar;17(2):235-47. doi: 10.1111/j.1369-1600.2010.00310.x. Epub 2011 Mar 11.


Growing evidence supports a role for the central nervous system (CNS) neurotransmitter L-glutamate and its metabotropic receptors (mGluRs) in drug addiction in general and alcohol-use disorders in particular. Alcohol dependence, for instance, has a genetic component, and the recent discovery that variations in the gene coding for mGluR7 modulate alcohol consumption further validates involvement of the L-glutamate system. Consequently, increasing interest emerges in developing L-glutamatergic therapies for the treatment of alcohol abuse and dependence. To this end, we performed a detailed behavioral pharmacology study to investigate the regulation of alcohol consumption and preference following administration of the mGluR7-selective drugs N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082) and 6-(4-Methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). Upon administration of the allosteric agonist AMN082 (10 mg/kg, i.p.) in rats, there was a significant decrease in ethanol consumption and preference, without affecting ethanol blood metabolism. In contrast, mGluR7 blockade with MMPIP (10 mg/kg, i.p.) showed an increase in alcohol intake and reversed AMN082's effect on ethanol consumption and preference. Both mGluR7-directed pharmacological tools had no effect on total fluid intake, taste preference, or on spontaneous locomotor activity. In conclusion, these findings support a specific regulatory role for mGluR7 on alcohol drinking and preference and provide evidence for the use of AMN082-type drugs as potential new treatments for alcohol-use disorders in man.

MeSH terms

  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / psychology
  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Ethanol / metabolism
  • Food Preferences / drug effects
  • Male
  • Motor Activity / drug effects
  • Pyridones / pharmacology*
  • Quinine / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors*
  • Saccharin / pharmacology
  • Self Administration
  • Sweetening Agents / pharmacology
  • Taste / drug effects


  • 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazonolo(4,5-c)pyridin-4(5H)-one
  • Benzhydryl Compounds
  • N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride
  • Pyridones
  • Receptors, Metabotropic Glutamate
  • Sweetening Agents
  • metabotropic glutamate receptor 7
  • Ethanol
  • Quinine
  • Saccharin