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向伏隔核注射γ-氨基丁酸激动剂对纳洛酮诱导的吗啡戒断反应的影响

Effects of Injection of Gamma-Aminobutyric Acid Agonists into the Nucleus Accumbens on Naloxone-Induced Morphine Withdrawal.

作者信息

Topkara Betilay, Yananli Hasan R, Sakallı Eren, Demirkapu Mahluga Jafarova

机构信息

Department of Pharmacology, Marmara University School of Medicine, Istanbul, Turkey.

出版信息

Pharmacology. 2017;100(3-4):131-138. doi: 10.1159/000477548. Epub 2017 Jun 22.

Abstract

AIMS

This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms.

METHODS

Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day.

RESULTS

Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups.

CONCLUSION

These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.

摘要

目的

本研究旨在探讨伏隔核(NAc)局部给予γ-氨基丁酸(GABA)激动剂对纳洛酮诱发的吗啡戒断症状的影响。

方法

将双侧引导套管立体定位植入Sprague-Dawley大鼠伏隔核的壳区或核心区。经过恢复期后,在研究的第一天和第三天,于轻度乙醚麻醉下将3颗吗啡丸(每颗含75mg吗啡碱)皮下植入大鼠体内。将GABA激动剂盐酸巴氯芬或氢溴酸蝇蕈醇注入伏隔核,并于第五天用纳洛酮诱发吗啡戒断。

结果

与对照组相比,向Sprague-Dawley大鼠伏隔核的壳区或核心区给予巴氯芬导致吗啡戒断期行为和运动活动参数在统计学上显著降低。然而,除了湿狗样抖动外,对照组和蝇蕈醇处理组之间的运动活动或戒断行为参数没有统计学上的显著变化。

结论

这些发现表明,伏隔核中的GABA能传导对吗啡戒断症状有效,且伏隔核的壳区和核心区均与这种效应相关。

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