Lou Zhong-ze, Chen Ling-hong, Liu Hui-feng, Ruan Lie-min, Zhou Wen-hua
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.
Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, Ningbo 315010, China.
Acta Pharmacol Sin. 2014 Dec;35(12):1485-92. doi: 10.1038/aps.2014.93. Epub 2014 Nov 17.
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.
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SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks.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.
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.
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.
伏隔核（NAc）中的谷氨酸能神经传递对于海洛因寻求行为的复发至关重要。本研究的目的是确定NAc核心或壳中的代谢型谷氨酸受体5（mGluR5）是否参与大鼠的海洛因寻求行为。
雄性SD大鼠在固定比率1（FR1）强化程序下自我给药海洛因14天，随后停药2周。然后在由环境、线索或海洛因引发诱导的海洛因寻求测试前10分钟，将选择性mGluR5拮抗剂2-甲基-6-苯基乙炔基吡啶（MPEP，每侧5、15和50 nmol）微量注射到NAc核心或壳中。
将MPEP微量注射到NAc壳中可剂量依赖性地减少由环境、线索或海洛因引发诱导的海洛因寻求行为。相比之下，将MPEP微量注射到NAc核心中并未改变由线索或海洛因引发诱导的海洛因寻求行为。此外，在NAc壳中微量注射MPEP（每侧15 nmol）可逆转海洛因戒断后开放臂进入百分比（OE%）和在开放臂中花费时间的百分比（OT%）。在作为对照部位的纹状体中微量注射MPEP（每侧50 nmol）不影响海洛因寻求行为。在这3个部位微量注射MPEP均未改变运动活动。
阻断大鼠NAc壳中的mGluR5可特异性抑制海洛因寻求行为的复发和焦虑样行为，提示mGluR5拮抗剂可能是治疗海洛因成瘾的潜在候选药物。
