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.
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.
Bäckström
Pia
P
Department of Mental Health and Alcohol Research, National Public Health Institute, P.O. Box 33, FI-00251 Helsinki, Finland.
Hyytiä
Petri
P
D000428:Alcohol Drinking / Q000517:prevention & control*; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008027:Light; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D012055:Reinforcement Schedule; D012646:Self Administration; D012903:Smell; D013997:Time Factors
C110733:3,4-dicarboxyphenylglycine; D000596:Amino Acids; D001565:Benzoates; D019086:Bridged Bicyclo Compounds, Heterocyclic; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C111435:metabotropic glutamate receptor 8; D000431:Ethanol; D005998:Glycine