Effects of γ-aminobutyric acid on feeding changes in rats and its potential mechanism

中华行为医学与脑科学杂志 Pub Date : 2019-11-20 DOI:10.3760/CMA.J.ISSN.1674-6554.2019.11.003

W. Qian, Leng Hui, L. Xiao, Guo Feifei, Sun Xiangrong, G. Shengli, Xu Luo

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Abstract

Objective To investigate whether γ-aminobutyric acid (GABA) receptor signaling pathway is involved in the regulation of thalamic undefined (ZI)-nucleus accumbens (NAc) neural pathways on gastric distraction (GD)-sensitive neuronal firing activity and the impact on food intake, the number of times and the frequency in rats. Methods Six rats were randomly selected and the neural pathway between ZI and NAc in rat thalamus was observed by fluorescent gold (FG) retrograde tracing method.Eighty-two rats were randomly selected, and the gastric balloon was placed in gastric cavity, the microelectrode was placed in the NAc, and the stimulating electrode was placed in the ZI. The single-cell discharge recording method was used to observe the effect of electrical stimulation ZI on the excitability of GD-sensitive neurons in rat NAc.Eighteen rats were randomly selected and were divided into three groups according to the random number table. They were NS group, GABA group, GABA + GABA receptor antagonist bicuculline (BIC) group with 6 in each group, and the rat NAc was used to embed the cannula. The method of GABA and BIC was injected to observe the changes of cumulative food intake in rats for 4 h. Eighteen rats were randomly selected and randomly divided into three groups: sham stimulation (SS) group, 50 μA electrical stimulation group, 50 μA electrical stimulation + BIC group with 6 in each group. The 4 h cumulative food intake of rats was observed by electro-stimulation of rat ZI and rat NAc injection of BIC. Results Fluorescent gold retrograde tracking combined with fluorescent immunohistochemical staining showed that there were visible GABA and fluorescent gold double labeled neurons in ZI. Electrical stimulation of ZI, the frequency of GABA-sensitive GD neurons in rat NAc increased significantly (GD-E increase: (78.8±8.4)%, GD-I increase: (89.3±9.2)%, P<0.01), but the inhibitory effect was antagonized by BIC (GD-E increase: (113.8±13.6)%, GD-I increase: (121.8±14.2)%, P<0.01). Microinjection of GABA in rat NAc significantly increased the cumulative food intake for 4 h ((155.72±18.84) kcal, t=3.41, P<0.05), which was antagonized by partial BIC (123.43±15.11) kcal, t=3.28, P<0.05). Electrical stimulation of ZI significantly increased the food intake in rats ((39.07±11.27) kcal, t=2.96, P<0.05), and this effect can be partially antagonized by BIC ((34.17±10.85)kcal, t=2.33, P<0.05). Conclusion The ZI-NAc neural pathway regulates the discharge activity of rat gastric distension (GD)-sensitive neurons and the feeding status of rats, and the GABA receptor signaling pathway may be involved in mediating the process. Key words: Zona incerta; Nucleus accumbens; γ-aminobutyric acid; Gastric distension-sensitive neurons; Feeding

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γ-氨基丁酸对大鼠摄食变化的影响及其可能机制

目的探讨γ-氨基丁酸(GABA)受体信号通路是否参与调节丘脑未定义(ZI)-伏隔核(NAc)神经通路对大鼠胃牵张(GD)敏感神经元放电活动的影响及其对进食量、次数和频率的影响。方法随机选取6只大鼠，采用荧光金(FG)逆行示踪法观察大鼠丘脑ZI与NAc之间的神经通路。随机选取82只大鼠，胃球囊置于胃腔内，微电极置于NAc内，刺激电极置于ZI内。采用单细胞放电记录法观察电刺激ZI对大鼠NAc中gd敏感神经元兴奋性的影响。随机选取18只大鼠，按随机数字表分为3组。分别为NS组、GABA组、GABA + GABA受体拮抗剂双丘碱(BIC)组，每组6只，采用大鼠NAc包埋插管。采用注射GABA + BIC的方法，观察大鼠4 h的累积进食量变化。随机选取18只大鼠，随机分为3组:假刺激(SS)组、50 μA电刺激组、50 μA电刺激+ BIC组，每组6只。通过电刺激大鼠ZI和大鼠NAc注射BIC，观察大鼠4 h的累积摄食量。结果荧光金逆行追踪结合荧光免疫组化染色显示，ZI中可见GABA和荧光金双标记神经元。电刺激ZI后，大鼠NAc中gaba敏感GD神经元的频率明显增加(GD- e增加(78.8±8.4)%，GD- i增加(89.3±9.2)%，P<0.01)，但BIC的抑制作用被拮抗(GD- e增加(113.8±13.6)%，GD- i增加(121.8±14.2)%，P<0.01)。微量注射GABA可显著增加NAc大鼠4 h的累积摄食量((155.72±18.84)kcal, t=3.41, P<0.05)，并可被部分BIC拮抗(123.43±15.11)kcal, t=3.28, P<0.05)。电刺激ZI可显著增加大鼠的摄食量((39.07±11.27)kcal, t=2.96, P<0.05)， BIC可部分拮抗((34.17±10.85)kcal, t=2.33, P<0.05)。结论ZI-NAc神经通路调节大鼠胃胀(GD)敏感神经元的放电活动和大鼠的进食状态，GABA受体信号通路可能参与了这一过程。关键词:无尾带;伏隔核;γ氨基丁酸酸;胃胀敏感神经元;喂养

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中华行为医学与脑科学杂志

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期刊介绍： "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.