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蓝斑核TRPV1受体在吗啡依赖的形成与表达中的作用。

The role of locus coeruleus nucleus TRPV1 receptors in the development and expression of morphine dependence.

作者信息

Fatemi Iman, Hadadianpour Zahra, Fatehi Farangis, Shamsizadeh Ali, Hasanshahi Jalal, Abbasifard Mitra, Kaeidi Ayat

机构信息

Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.

Physiology-pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

出版信息

Iran J Basic Med Sci. 2019 Oct;22(10):1186-1191. doi: 10.22038/ijbms.2019.35055.8338.

Abstract

OBJECTIVES

This study investigated the role of locus coeruleus (LC) nucleus TRPV1 receptors (TRPV1r) in the expression and development of morphine physical dependence by intra-LC administration of AMG9810 (selective TRPV1r antagonist) in male Wistar rats.

MATERIALS AND METHODS

For assessing the development of morphine dependence, AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered before each morphine administration for seven continues days (once daily; 6, 16, 26, 36, 46, 56, and 66 mg/kg; sc). Furthermore, for evaluating the expression of morphine dependence, a single dose of AMG9810 (0.03 and 0.3 mM in 10% DMSO, 0.2 µl; intra-LC microinjection) was administered to morphine-dependent rats on day 8 of the experiment.

RESULTS

Obtained data demonstrated that co-administration of TRPV1r antagonist with morphine reduced the development of morphine withdrawal syndrome somatic signs induced by naloxone. Moreover, single intra-LC administration of TRPV1r antagonist on the final day of the examination period significantly decreased the expression of some signs of morphine withdrawal in rats.

CONCLUSION

The results showed that LC TRPV1r might be participating in the expression and development of morphine dependence.

摘要

目的

本研究通过向雄性Wistar大鼠脑桥蓝斑核(LC)内注射AMG9810(选择性瞬时受体电位香草酸亚型1受体拮抗剂,TRPV1r),研究LC核内TRPV1r在吗啡身体依赖性的表达和发展中的作用。

材料与方法

为评估吗啡依赖性的发展,在连续7天每天一次皮下注射吗啡(6、16、26、36、46、56和66mg/kg)前,均向LC内注射AMG9810(10%二甲基亚砜中0.03和0.3mM,0.2μl;LC内微量注射)。此外,为评估吗啡依赖性的表达,在实验第8天,向吗啡依赖大鼠单次LC内注射AMG9810(10%二甲基亚砜中0.03和0.3mM,0.2μl;LC内微量注射)。

结果

所得数据表明,TRPV1r拮抗剂与吗啡共同给药可减轻纳洛酮诱发的吗啡戒断综合征躯体症状的发展。此外,在检查期最后一天单次LC内注射TRPV1r拮抗剂可显著降低大鼠吗啡戒断某些症状的表达。

结论

结果表明,LC TRPV1r可能参与吗啡依赖性的表达和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1e3/6885386/2db5655e4979/IJBMS-22-1186-g001.jpg

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