Murray T F, McGill W, Cheney D L
Eur J Pharmacol. 1983 Jun 3;90(2-3):179-84. doi: 10.1016/0014-2999(83)90235-2.
Both the gamma-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[ 1-piperazinyl ]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
γ-氨基丁酸（GABA）模拟物THIP（4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇）和血清素能激动剂MK 212（6-氯-2-[1-哌嗪基]吡嗪）在小鼠热板试验中都是有效的镇痛剂。然而，纳曲酮不能逆转这两种化合物引起的镇痛作用。急性注射THIP可增强吗啡的镇痛作用，长期给予THIP会对其镇痛效果产生功能性耐受。MK 212可拮抗由吗啡或THIP诱导的镇痛作用。这些结果支持这样的假设，即GABA能和血清素能突触代表两种突触机制，它们以独立于阿片受体的方式参与疼痛阈值的调节。此外，GABA和血清素似乎能够以相反的方式调节阿片介导的镇痛作用，GABA能机制促进而血清素能机制抑制吗啡诱导的抗伤害感受。
