MONOAMINERGIC MECHANISMS OF STIMULATION-PRODUCED ANALGESIA
MONOAMINERGIC MECHANISMS OF STIMULATION-PRODUCED ANALGESIA
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DOI：
10.1016/0006-8993(75)90062-1
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发表时间：
1975-01-01
期刊：
影响因子：
2.9
通讯作者：
LIEBESKIND, JC
中科院分区：
文献类型：
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作者：
AKIL, H;LIEBESKIND, JC
采用甩尾试验对大鼠中脑单胺（多巴胺、去甲肾上腺素和血清素）在刺激镇痛 (SPA) 中的作用进行了研究。 SPA 是通过长期植入中脑导水管周围灰质的双极电极引发的，该区域先前已被证明可以产生有效且可靠的镇痛效果。使用四种方法来改变单胺途径的传递。(1)通过给予丁苯那嗪 (TBZ)、对氯苯丙氨酸 (PCPA)、α-甲基-对酪氨酸 (AMPT) 或双硫仑来消耗单胺。(2)用适当的前体（5-HTP 或 l-DOPA）与外周脱羧酶抑制剂组合来替代消耗的单胺储存。(3)通过给先前未治疗的动物施用前体或通过施用多巴胺受体刺激剂阿朴吗啡来建立单胺系统。(4)用氟哌啶醇阻断儿茶酚胺受体或用匹莫齐特阻断巴胺受体。这4种方法产生了内部一致的结果。所有3种单胺(TBZ)的耗尽导致了SPA的强大抑制。通过注射 5-HTP 或 1-DOPA 可恢复 SPA 的原始水平。特异性消耗血清素 (PCPA) 会导致 SPA 减少，而血清素水平 (5-HTP) 升高会导致 SPA 增加。多巴胺受体阻断剂（匹莫齐特）会减少 SPA，而前体（l-DOPA）和多巴胺受体刺激剂（阿朴吗啡）会增加 SPA。另一方面，选择性去甲肾上腺素（双硫仑）的消耗导致 SPA 增加；并且，当去甲肾上腺素水平降低且多巴胺水平升高（AMPT+l-DOPA）时，SPA被认为特别增强。
The roles played by the cerebral monoamines (dopamine, noradrenaline and serotonin) in stimulation-produced analgesia (SPA) have been investigated in the rat employing the tail flick test. SPA was elicited through bipolar electrodes chronically implanted in the mesencephalic periaqueductal gray matter, an area previously shown to yield potent and reliable analgesic effects. Four approaches were used to alter transmission in monoamine pathways.(1)Depletionof monoamines by administration of tetrabenazine (TBZ),p-chlorophenylalanine (PCPA), alpha-methyl-para-tyrosine (AMPT), or disulfiram.(2)Replacementof depleted monoamine stores by appropriate precursors (5-HTP orl-DOPA) in combination with a peripheral decar☐ylase inhibitor.(3)Potentiationof monoamine systems by administration of precursors to previously untreated animals or by administration of a dopamine receptor stimulator, apomorphine.(4)Blockadeof catecholamine receptors by haloperidol or of opamine receptors by pimozide.These 4 approaches yielded internally consistent results.Depletion of all 3 monoamines (TBZ) led to a powerful inhibition of SPA. Original levels of SPA were restored by injection of either 5-HTP orl-DOPA.Specific depletion of serotonin (PCPA) caused a reduction in SPA, whereas elevation of serotonin levels (5-HTP) caused an increase in SPA.Dopamine receptor blockade (pimozide) decreased SPA, whereas the precursor (l-DOPA) and a dopamine receptor stimulator (apomorphine) increased SPA.On the other hand, selective depletion of noradrenaline (disulfiram) caused anincreasein SPA; and, at a time when noradrenaline levels are depressed and dopamine levels are elevated (AMPT +l-DOPA), SPA was seen to be particularly enhanced.