Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats

• Published in: Acta pharmacologica Sinica Vol. 35; no. 12; pp. 1485 - 1492
• Main Authors: Lou, Zhong-ze, Chen, Ling-hong, Liu, Hui-feng, Ruan, Lie-min, Zhou, Wen-hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2014; Nature Publishing Group
• Subjects: Analgesics, Opioid - administration & dosage; Animals; Anxiety - drug therapy; Anxiety - metabolism; Anxiety - psychology; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; Cues; Dose-Response Relationship, Drug; Drug-Seeking Behavior - drug effects; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Heroin - administration & dosage; Heroin Dependence - drug therapy; Heroin Dependence - metabolism; Heroin Dependence - psychology; Immunology; Internal Medicine; Locomotion - drug effects; Male; Medical Microbiology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Original; original-article; Pharmacology/Toxicology; Pyridines - administration & dosage; Pyridines - pharmacology; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5 - antagonists & inhibitors; Receptor, Metabotropic Glutamate 5 - metabolism; Recurrence; SD大鼠; Self Administration; Substance Withdrawal Syndrome - drug therapy; Substance Withdrawal Syndrome - metabolism; Substance Withdrawal Syndrome - psychology; Time Factors; Vaccine; 伏隔核; 外壳; 封锁; 注射剂量; 海洛因; 神经传递; 行为; heroin; striatum; relapse; the nucleus accumbens; addiction; MPEP; mGluR5
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2014.93

Aim： 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SD rats were self-administered heroin under a fixed-ratio 1 （FR1） reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks.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 perside） 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. Conclusion： 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.