大鼠中脑导水管周围灰质腹侧微量注射吗啡镇痛作用的γ-氨基丁酸能调节

GABAergic modulation of the analgesic effects of morphine microinjected in the ventral periaqueductal gray matter of the rat.

作者信息

Depaulis A, Morgan M M, Liebeskind J C

机构信息

Department of Psychology, University of California, Los Angeles 90024.

出版信息

Brain Res. 1987 Dec 15;436(2):223-8. doi: 10.1016/0006-8993(87)91665-9.

DOI:10.1016/0006-8993(87)91665-9

PMID:3435824

Abstract

The possibility that GABAergic neurons in the ventral periaqueductal gray matter modulate the analgesic effects of morphine microinjected into this brain area was investigated in the rat. Microinjection of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin 3-ol (THIP) (0.4 microgram in 0.2 microliter), a GABA agonist, in the ventral periaqueductal gray matter significantly reversed the increase of tail-flick latency induced by a prior injection of morphine sulfate (4 micrograms in 0.2 microliter) at the same site. Conversely, microinjection in the same region of picrotoxin (10 ng in 0.2 microliter), a GABA antagonist, significantly potentiated the analgesic effect of the same dose of morphine. These results suggest the existence of GABAergic neurons that tonically inhibit periaqueductal gray output neurons involved in centrifugal pain inhibition. The analgesic effects of opiates may, at least in part, result from disinhibition of these GABAergic neurons.

摘要

在大鼠中研究了腹侧导水管周围灰质中的γ-氨基丁酸（GABA）能神经元调节向该脑区微量注射吗啡的镇痛作用的可能性。向腹侧导水管周围灰质微量注射GABA激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇（THIP）（0.2微升中含0.4微克），可显著逆转先前在同一部位注射硫酸吗啡（0.2微升中含4微克）所诱导的甩尾潜伏期的延长。相反，向同一区域微量注射GABA拮抗剂苦味毒（0.2微升中含10纳克），可显著增强相同剂量吗啡的镇痛作用。这些结果表明，存在对参与离心性疼痛抑制的导水管周围灰质输出神经元进行紧张性抑制的GABA能神经元。阿片类药物的镇痛作用可能至少部分源于这些GABA能神经元的去抑制作用。