Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG

Eur J Pharmacol. 2005 Dec 28;528(1-3):110-8. doi: 10.1016/j.ejphar.2005.10.051. Epub 2005 Dec 1.

Abstract

Glutamatergic neurotransmission has been suggested to modulate cue-induced drug-seeking behavior. Here we examined the effects of metabotropic glutamate receptor agonists on alcohol self-administration and cue-induced reinstatement. Rats were trained to self-administer 10% w/v ethanol under an FR1 schedule of reinforcement during 30-min sessions. In the reinstatement experiments, ethanol and a non-rewarding quinine solution (available on alternating days) were paired with olfactory stimuli (S+/S-) as well as light (CS+) or tone (CS-) stimuli. Following extinction training, reinstatement of responding was induced by the ethanol-associated stimuli (S+/CS+). The mGlu2/3 receptor agonist LY379268 (0, 1, 3 and 5 mg/kg i.p.) and the mGlu8 receptor agonist (S)-3,4-DCPG (0, 5, 10 and 15 mg/kg i.p.) attenuated alcohol self-administration and reinstatement at doses that decreased also spontaneous locomotor activity. The results suggest that metabotropic glutamate receptors may have a role in the modulation of alcohol seeking and self-administration. However, further studies with ligands with fewer motor-suppressant side effects are needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / prevention & control*
  • Amino Acids / pharmacology*
  • Animals
  • Behavior, Addictive / prevention & control
  • Behavior, Animal / drug effects*
  • Benzoates / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology*
  • Conditioning, Operant / drug effects
  • Cues
  • Dose-Response Relationship, Drug
  • Ethanol / administration & dosage
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Light
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Long-Evans
  • Receptors, Metabotropic Glutamate / agonists*
  • Reinforcement Schedule
  • Self Administration
  • Smell
  • Time Factors

Substances

  • 3,4-dicarboxyphenylglycine
  • Amino Acids
  • Benzoates
  • Bridged Bicyclo Compounds, Heterocyclic
  • LY 379268
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • metabotropic glutamate receptor 8
  • Ethanol
  • Glycine