Local effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus.

Local effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus.
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DOI:
10.1016/s0014-2999(98)00374-4
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发表时间:
1998-07
影响因子:
5
通讯作者:
Adrienne S. Miller;J. Michael Walker
Adrienne S. Miller;J. Michael Walker
中科院分区:
医学2区
文献类型:
--
作者:
Adrienne S. Miller;J. Michael Walker

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苍白球已被确定为大麻素运动效应的作用部位。来自该实验室的先前报告表明,全身施用有效的和选择性的大麻素受体激动剂(R)-(+)-[2,3-二氢-5-甲基-3-[(4-吗啉基)甲基]吡咯并[1,2,3-de]-1,4-苯并恶嗪-6-基](1-萘基)甲酮(WIN 55,212 -2)抑制大鼠苍白球神经元并逆转由纹状体的电刺激产生的苍白球活性的抑制。目前的研究使用在体内单单位电生理/微压喷射,以调查大麻素对苍白球的自发活动和诱发抑制的影响是否是局部介导的。将WIN 55,212 -2或CP 55,940微压喷射到苍白球中可抑制苍白球中的自发活动。大麻素受体拮抗剂N-哌啶基-5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-3-吡唑-甲酰胺(SR 141716 A)的局部给药对其自身没有产生影响,但阻断了WIN 55,212 -2对苍白球神经元自发活动的影响。由WIN 55,212 -2引起的苍白球活性的降低并不被荷包牡丹碱的联合给药所阻断,表明这种作用不依赖于GABA A受体。微压喷射大麻素到苍白球并没有逆转纹状体刺激苍白球的抑制作用。两者合计,这些研究结果表明,苍白球大麻素受体介导的抑制苍白球的自发活动。
The globus pallidus has been identified as a site of action for the motor effects of cannabinoids. A previous report from this laboratory demonstrated that systemic administration of the potent and selective cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl] (1-napthalenyl) methanone (WIN 55,212-2) inhibits rat pallidal neurons and reverses the inhibition of pallidal activity produced by electrical stimulation of the striatum. The current study used in vivo single unit electrophysiology/micropressure ejection to investigate whether the effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus are locally mediated. Micropressure ejection of either WIN 55,212-2 or CP 55,940 into the globus pallidus inhibited spontaneous activity in the globus pallidus. Local administration of the cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A), did not produce an effect on its own but blocked the effect of WIN 55,212-2 on spontaneous activity of pallidal neurons. The decrease in pallidal activity produced by WIN 55,212-2 was not blocked by coadministration of bicuculline, suggesting this effect is independent of GABAAreceptors. Micropressure ejection of cannabinoids into the globus pallidus did not reverse the inhibitory effect of striatal stimulation in the globus pallidus. Taken together, these findings suggest that pallidal cannabinoid receptors mediate an inhibition of spontaneous activity in the globus pallidus.