Hernandez D E, Drago F, Mason G A, Stanley D A, Prange A J
Pharmacol Biochem Behav. 1986 Mar;24(3):425-8. doi: 10.1016/0091-3057(86)90535-6.
In previous reports, we have demonstrated that intracisternal (IC) administration of neurotensin (NT), an endogenous tridecapeptide, produces significant antinociception in a variety of analgesic tests, including the hot-plate test. In addition, many of the central nervous system effects of NT (i.e., hypothermia, gastric cytoprotection) appear to be mediated by brain dopamine (DA) systems. In this study, we evaluated the effect of selected DA agonists and antagonists on NT-induced antinociception in the hot-plate test with mice. Doses, route of administration, and pretreatment interval were determined from the available literature to significantly affect the incidence of DA-dependent behaviors. Pretreatment with chlorpromazine but not haloperidol significantly potentiated NT-induced antinociception. This potentiating effect of chlorpromazine appears not to be due to any intrinsic antinociceptive activity of this agent, chlorpromazine had no significant effect on hot-plate latencies when administered alone. The involvement of DA on NT-induced antinociception was further substantiated by the findings that pretreatment with several DA receptor agonists, including methylphenidate, apomorphine, and d-amphetamine, significantly antagonized the antinociceptive response to IC NT. None of these agents significantly altered the animal's response to the hot-plate when administered alone. The data furnished in the present report suggest that central DA circuits may be involved in the expression of NT-induced antinociception.
在先前的报告中，我们已经证明，脑池内（IC）注射神经降压素（NT，一种内源性十三肽）在包括热板试验在内的多种镇痛试验中能产生显著的镇痛作用。此外，NT的许多中枢神经系统效应（即体温过低、胃细胞保护）似乎是由脑多巴胺（DA）系统介导的。在本研究中，我们评估了所选的DA激动剂和拮抗剂对小鼠热板试验中NT诱导的镇痛作用的影响。根据现有文献确定了剂量、给药途径和预处理间隔，这些因素会显著影响依赖DA的行为发生率。用氯丙嗪而非氟哌啶醇预处理可显著增强NT诱导的镇痛作用。氯丙嗪的这种增强作用似乎并非由于该药物本身具有任何内在的镇痛活性，因为单独给予氯丙嗪时对热板潜伏期没有显著影响。几种DA受体激动剂，包括哌醋甲酯、阿扑吗啡和右旋苯丙胺，预处理后可显著拮抗对IC NT的镇痛反应，这一发现进一步证实了DA参与NT诱导的镇痛作用。这些药物单独给药时均未显著改变动物对热板的反应。本报告提供的数据表明，中枢DA回路可能参与了NT诱导的镇痛作用的表达。
