前边缘皮质生长激素抑制素神经元在吗啡引起的行为学改变中的作用
侯伟青, 刘佩佩, 王雪颖, 马兰, 王菲菲^*
复旦大学基础医学院医学神经生物学国家重点实验室，药理研究中心，上海 200032
摘要
药物成瘾是一种由药物滥用所引起的慢性、复发性的精神疾病，主要特征是不计后果的强迫性用药。药物成瘾涉及多个脑区的神经可塑性改变。前边缘皮质(prelimbic cortex, PrL)是背内侧前额叶皮质的主要区域，有大量的锥体神经元，其兴奋性神经投射可以促进可卡因觅药行为。PrL还存在少量GABA能中间神经元，对PrL的兴奋性神经元功能、信息整合和传递起到重要的调控作用，而这一部分神经元在药物成瘾过程中的作用并不清楚。小清蛋白(parvalbumin, PV)和生长激素抑制素(somatostatin, SST)神经元是前额叶皮质中分布广泛的两类主要的抑制性GABA能中间神经元。本研究利用PV-Cre和SST-Cre的转基因小鼠，结合化学遗传学的方法探究PrL中间神经元在吗啡引起的行为学改变中的作用。结果显示，特异性抑制PrL脑区SST神经元可以显著增加小鼠的焦虑水平，但不影响小鼠的运动能力；抑制PrL脑区SST神经元降低小鼠吗啡诱导的活动性增强及条件位置偏爱；而抑制PrL脑区PV神经元则对小鼠的运动能力、焦虑水平及吗啡引起的行为学改变均没有显著影响。本研究通过对PrL脑区PV及SST中间神经元在吗啡诱导的行为学改变中作用的研究，为成瘾药物作用的细胞及神经基础提供了依据。


关键词： 前边缘皮质; PV中间神经元; SST中间神经元; 吗啡; 条件位置偏爱
分类号：R964

Somatostatin interneurons of prelimbic cortex in regulating morphine- induced behavior changes
HOU Wei-Qing, LIU Pei-Pei, WANG Xue-Ying, Ma Lan, WANG Fei-Fei^*
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
Abstract
Drug addiction is a chronic psychiatric disorder characterized by compulsive drug taking, and involves neuronal plasticity changes in multiple brain regions. The prelimbic cortex (PrL) is a key region of the dorsomedial prefrontal cortex and contains majority of pyramidal neurons. The excitatory projections from PrL play a very important role in the drug seeking behaviors. PrL also contains a small amount of GABAergic interneurons, which regulate the information integration and transmission of the pyramidal neurons. However, the roles of the GABAergic interneurons in PrL in drug-induced behavior changes are not clear. In the PrL, parvalbumin (PV) and somatostatin (SST) interneurons are two major GABAergic interneurons, which have been reported to regulate the activity of glutamatergic input, and form inhibitory synaptic transmission to regulate the output of downstream signals. Here, we used PV-Cre and SST-Cre mice combined with chemical genetics to explore the role of PV and SST interneurons in PrL in morphine-induced behavior changes. Our data showed that specific inhibiting SST interneurons in PrL significantly increased the anxiety level and decreased morphine-induced locomotor activity and the conditioned place preference (CPP) score. Instead, specific inhibiting PV interneurons in PrL had no effect on the anxiety level, morphine induced-locomotor activity and CPP. Our findings provide a new insight into the cellular and neuronal specific mechanism for drug addiction.


Key words: prelimbic cortex; PV interneuron; SST interneuron; morphine; conditioned place preference

收稿日期：2018-05-15　　录用日期：2018-08-29
通讯作者：王菲菲　　E-mail: ffwang@fudan.edu.cn
DOI: 10.13294/j.aps.2018.0066
引用本文：
侯伟青, 刘佩佩, 王雪颖, 马兰, 王菲菲. 前边缘皮质生长激素抑制素神经元在吗啡引起的行为学改变中的作用[J]. 生理学报 2018; 70 (5): 463-473.
HOU Wei-Qing, LIU Pei-Pei, WANG Xue-Ying, Ma Lan, WANG Fei-Fei. Somatostatin interneurons of prelimbic cortex in regulating morphine- induced behavior changes. Acta Physiol Sin 2018; 70 (5): 463-473 (in Chinese with English abstract).



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