Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats.
OBJECTIVE
Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats.


METHODS
Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming.


RESULTS
Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities.


CONCLUSIONS
Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.
1] Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China [2] Department of Mental Health, Ningbo First Hospital, Ningbo 315010, China.
Zhong-ze
ZZ
Lou
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China.
Ling-hong
LH
Chen
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China.
Hui-feng
HF
Liu
Department of Mental Health, Ningbo First Hospital, Ningbo 315010, China.
Lie-min
LM
Ruan
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China.
Wen-hua
WH
Zhou
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012008:Recurrence; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D013997:Time Factors
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D003932:Heroin; C121465:6-methyl-2-(phenylethynyl)pyridine