The novel mGluR2/3 agonist LY379268 attenuates cue-induced reinstatement of heroin seeking.
In humans, drug-associated stimuli can provoke heroin relapse during abstinence. In rats, cues paired with heroin self-administration reinstate heroin seeking in a relapse model. The neurobiological mechanisms involved in this reinstatement, however, are largely unknown. Here, we determined the effect of LY379268, an mGluR2/3 agonist that decreases evoked glutamate release, on cue-induced reinstatement of heroin seeking. Systemic injections of LY379268 attenuated reinstatement of heroin seeking induced by exposure to a discrete tone-light cue that was previously paired with heroin infusions during self-administration training. In contrast, LY379268 had no effect on heroin self-administration. Results indicate that glutamate plays an important role in cue-induced reinstatement of heroin seeking and suggest that mGluR2/3 agonists should be considered for the treatment of opiate relapse.
Bossert
Jennifer M
JM
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. jbossert@intra.nida.nih.gov
Busch
Robert F
RF
Gray
Sarah M
SM
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009294:Narcotics / Q000008:administration & dosage; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration / Q000379:methods
D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018690:Excitatory Amino Acid Agonists; C118218:LY 379268; D009294:Narcotics; D003932:Heroin