A potential cholinergic mechanism of procaine's limbic activation
A potential cholinergic mechanism of procaine's limbic activation
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DOI：
10.1038/sj.npp.1300404
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发表时间：
2004-07-01
影响因子：
7.6
通讯作者：
Ketter, TA
中科院分区：
文献类型：
--
作者：
Benson, BE;Carson, RE;Ketter, TA
局部麻醉剂普鲁卡因，当静脉内（i.v）给药于人类时，产生短暂的强烈情感和感觉体验，并伴随着前边缘脑血流量的增加，如正电子发射断层扫描（PET）所测量的。普鲁卡因的高毒蕈碱亲和力，以及与普鲁卡因激活的脑区重叠的毒蕈碱受体的分布，表明毒蕈碱对普鲁卡因的情感和感觉效应有贡献。本研究评估了普鲁卡因对麻醉恒河猴大脑毒蕈碱胆碱能受体的影响。在同一天普鲁卡因给药前后，用PET和放射性示踪剂3-（3-（3[F-18]氟丙硫基）-1，2，5-噻二唑-4-基）-1，2，5，6-四氢-1-甲基吡啶（[F-18]FP-TZTP）（一种优先结合毒蕈碱（M-2）受体的胆碱能配体）测量了3只麻醉恒河猴的全脑和局部毒蕈碱受体结合。在不同的日子，每只动物以随机方式接受6种不同剂量的普鲁卡因静脉注射。普鲁卡因对[F-18]FP-TZTP特异性结合的阻断率约为90%，且呈剂量相关性。普鲁卡因对[F-18]FP-TZTP的50%阻断抑制浓度（IC_（50））无区域差异。在先前的猴研究中与脑血流量高度相关的示踪剂递送在普鲁卡因的所有剂量下均显著增加，其中最大增加发生在普鲁卡因的平均皮质的IC 50附近。此外，前边缘区域显示出比非边缘区域更大的示踪剂递送增加。在恒河猴体内，普鲁卡因对毒蕈碱M-2受体具有高亲和力。这一点，以及优先增加的示踪剂交付到边缘区域，表明这些受体的行动可能有助于静脉普鲁卡因的情绪和感官的影响man. These研究结果是一致的情绪和情绪的胆碱能调节的其他证据。
The local anesthetic procaine, when administered to humans intravenously (i.v,), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[F-18]fluoropropyithio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([F-18]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M-2) receptors. On separate days each animal received six different doses of i.v, procaine in a randomized fashion. Procaine blocked up to similar to90% of [F-18]FP-TZTP specific binding globally in a dose-related manner, There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC50) for [F-18]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC50 for average cortex, Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M-2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion.