ly-379268 and 3-4-dicarboxyphenylglycine

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.

Topics: Alcohol Drinking; Amino Acids; Animals; Behavior, Addictive; Behavior, Animal; Benzoates; Bridged Bicyclo Compounds, Heterocyclic; Conditioning, Operant; Cues; Dose-Response Relationship, Drug; Ethanol; Glycine; Light; Male; Motor Activity; Rats; Rats, Long-Evans; Receptors, Metabotropic Glutamate; Reinforcement Schedule; Self Administration; Smell; Time Factors