The group II metabotropic glutamate receptor agonist, LY379268, decreases methamphetamine self-administration in rats

Drug Alcohol Depend. 2013 Oct 1;132(3):414-9. doi: 10.1016/j.drugalcdep.2013.07.024. Epub 2013 Aug 2.


Background: Given the problems associated with the escalation in methamphetamine (METH) use, the identification of more effective treatment strategies is essential. Group II metabotropic glutamate receptors (mGluRs) have been suggested to be a novel therapeutic target for psychostimulant addiction. We sought to test the ability of the selective group II mGluR agonist LY379268 to reduce METH self-administration in rats.

Methods: Rats were trained to self-administer METH on a progressive ratio (PR) schedule. Animals were then switched to fixed ratio responding and given daily extended access (6 h/day) to METH self-administration for 14 days. Rats were then re-tested on the PR schedule. The effect of LY379268 on METH-reinforced PR responding was determined before and after 14 days of extended access. To test for non-specific effects, a separate group of animals received LY379268 prior to a sucrose pellet-reinforced PR schedule.

Results: Animals escalated their daily intake of METH during extended access. PR responding did not change as a function of extended access. LY379268 significantly attenuated METH reinforced responding, both before and after extended access. The degree of attenuation did not change as a function of extended access. LY379268 had no effect on sucrose pellet-reinforced responding at any dose.

Conclusions: LY379268 selectively reduced the motivation to self-administer METH. In contrast to data with other compounds, the sensitivity to the effects of LY379268 did not change following extended access to METH self-administration. Group II mGluR agonists, therefore, may represent a relatively new class of compounds for the development of pharmacotherapies for METH addiction.

Keywords: Extended-access; LY369268; Methamphetamine; Self-administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / pharmacology*
  • Amino Acids / therapeutic use*
  • Animals
  • Behavior, Addictive / prevention & control*
  • Behavior, Addictive / psychology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Dose-Response Relationship, Drug
  • Male
  • Methamphetamine / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / agonists*
  • Receptors, Metabotropic Glutamate / physiology
  • Self Administration


  • Amino Acids
  • Bridged Bicyclo Compounds, Heterocyclic
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • Methamphetamine