Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats
Abstract
Zhong-ze LOU1, 2, Ling-hong CHEN1, Hui-feng LIU1, Lie-min RUAN2, *, Wen-hua ZHOU1, *
1Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China; 2Department of Mental Health, Ningbo First Hospital, Ningbo 315010, China
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SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks.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 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.
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.
Keywords: heroin; addiction; relapse; mGluR5; MPEP; the nucleus accumbens; striatum
This work was supported by the National Key Technology R&D Program in the 12th Five-Year Plan of China (No 2012BAI01B07) and the National Natural Science Foundation of China (No U1132602 and 81171257), and was sponsored by the K C WONG Magna Fund at Ningbo University.
* To whom correspondence should be addressed.
E-mail lmruan@tom.com (Lie-min RUAN); whzhou@vip.163.com (Wen-hua ZHOU)
Received 2013-12-13 Accepted 2014-08-20
Keywords:
1Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China; 2Department of Mental Health, Ningbo First Hospital, Ningbo 315010, China
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 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.
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.
Keywords: heroin; addiction; relapse; mGluR5; MPEP; the nucleus accumbens; striatum
This work was supported by the National Key Technology R&D Program in the 12th Five-Year Plan of China (No 2012BAI01B07) and the National Natural Science Foundation of China (No U1132602 and 81171257), and was sponsored by the K C WONG Magna Fund at Ningbo University.
* To whom correspondence should be addressed.
E-mail lmruan@tom.com (Lie-min RUAN); whzhou@vip.163.com (Wen-hua ZHOU)
Received 2013-12-13 Accepted 2014-08-20