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黑质纹状体神经支配丧失改变大麻素对大鼠丘脑底核神经元活动的影响。

Nigrostriatal denervation changes the effect of cannabinoids on subthalamic neuronal activity in rats.

机构信息

Department of Pharmacology, Faculty of Medicine, University of the Basque Country, 48940, Leioa, Vizcaya, Spain.

出版信息

Psychopharmacology (Berl). 2011 Mar;214(2):379-89. doi: 10.1007/s00213-010-2043-0. Epub 2010 Oct 20.

DOI:10.1007/s00213-010-2043-0
PMID:20959968
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3045509/
Abstract

RATIONALE

It is known that dopaminergic cell loss leads to increased endogenous cannabinoid levels and CB1 receptor density.

OBJECTIVE

The aim of this study was to evaluate the influence of dopaminergic cell loss, induced by injection of 6-hydroxydopamine, on the effects exerted by cannabinoid agonists on neuron activity in the subthalamic nucleus (STN) of anesthetized rats.

RESULTS

We have previously shown that Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and anandamide induce both stimulation and inhibition of STN neuron activity and that endocannabinoids mediate tonic control of STN activity. Here, we show that in intact rats, the cannabinoid agonist WIN 55,212-2 stimulated all recorded STN neurons. Conversely, after dopaminergic depletion, WIN 55,212-2, Δ(9)-THC, or anandamide inhibited the STN firing rate without altering its discharge pattern, and stimulatory effects were not observed. Moreover, anandamide exerted a more intense inhibitory effect in lesioned rats in comparison to control rats.

CONCLUSIONS

Cannabinoids induce different effects on the STN depending on the integrity of the nigrostriatal pathway. These findings advance our understanding of the role of cannabinoids in diseases involving dopamine deficits.

摘要

原理

已知多巴胺能神经元的丧失会导致内源性大麻素水平和 CB1 受体密度增加。

目的

本研究旨在评估多巴胺能神经元丧失（通过注射 6-羟多巴胺诱导）对大麻素激动剂对麻醉大鼠丘脑底核（STN）神经元活动的影响。

结果

我们之前已经表明，Δ(9)-四氢大麻酚（Δ(9)-THC）和花生四烯酸酰胺既诱导 STN 神经元活动的刺激又抑制，并且内源性大麻素介导 STN 活动的紧张性控制。在这里，我们表明在完整的大鼠中，大麻素激动剂 WIN 55,212-2 刺激所有记录的 STN 神经元。相反，在多巴胺能耗竭后，WIN 55,212-2、Δ(9)-THC 或花生四烯酸酰胺抑制 STN 放电率而不改变其放电模式，并且没有观察到刺激作用。此外，与对照组大鼠相比，损伤大鼠中花生四烯酸酰胺表现出更强的抑制作用。

结论

大麻素根据黑质纹状体通路的完整性对 STN 产生不同的影响。这些发现增进了我们对涉及多巴胺缺乏的疾病中大麻素作用的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/1fa774d0eee6/213_2010_2043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/3762098dc9ab/213_2010_2043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/79e8509d25ab/213_2010_2043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/9ce5dca2ec14/213_2010_2043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/aac99ad6e19a/213_2010_2043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/1fa774d0eee6/213_2010_2043_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/3762098dc9ab/213_2010_2043_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/79e8509d25ab/213_2010_2043_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/9ce5dca2ec14/213_2010_2043_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/aac99ad6e19a/213_2010_2043_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c211/3045509/1fa774d0eee6/213_2010_2043_Fig5_HTML.jpg

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