Different mechanism of the antinociceptive effects of morphine and dermorphin tetrapeptide analogs

1)我们研究了MU1-阿片受体在吗啡和德吗啡四肽类似物诱导的抗伤害性反应中的作用，在小鼠中以冈上调节的行为(不包括脊髓反射)为标准。鞘内(I.T.)在尾压试验中，给予吗啡作为机械伤害性刺激，产生了强烈而显著的抗伤害性反应。3)在化学伤害性刺激的福尔马林实验中，尾静脉注射纳洛酮对舔咬反应有明显的抑制作用。和IT。注射了吗啡。4)在热板实验中，纳洛酮作为一种热伤害性刺激，两者均被i.c.v。和IT。预先给予纳洛酮可显著降低吗啡的抗伤害性反应。5)纳洛酮可拮抗两种侧脑室注射吗啡的抗伤害性反应。和IT。德吗啡四肽类似物(H-Tyr-Darg-Phe-beta-Ala：Tapa)对抗机械刺激和化学刺激的反应。6)尽管预先给予纳洛酮不能拮抗i.c.v的抗伤害感受活性。Tapa-NH2对机械和化学有害刺激和I.T.Tapa-NH2对机械伤害性刺激，I.T.Naloxonazine可显著降低TAPA-NH2对化学刺激的抗伤害作用。

1) We investigated the role of mu1-opioid receptors on morphine-and dermorphin tetrapeptide analogs-induced antinociception using supraspinally mediated behavours exclusive of the spinal reflex as criteria in mice.2) Both intracerebroventricular (i.c.v.) and intrathecal (i.t.) administered morphine produced potent and significant antinociceptive activity in the tail-pressure test as a mechanical noxious stimulus. The pretreatment with naloxonazine failed to antagonize the activity.3) In the formalin test as a chemical noxious stimulus, licking and biting response was significantly inhibited by both i.c.v. and i.t. administered morphine. The activity was remarkably diminished by naloxonazine.4) In the hot plate test as a thermal noxious stimulus, both i.c.v. and i.t. administered-morphine induced antiniciceptive activity was significantly reduced by the pretreatment with naloxonazine.5) Pretreatment with naloxonazine antagonized the antinociceptive effects of both i.c.v. and i.t. dermorphin tetrapeptide analog (H-Tyr-DArg-Phe-beta-ala : TAPA) against response to mechanical and chemical stimuli.6) Although the pretreatment with naloxonazine was not antagonized the antinociceptive activity of i.c.v. TAPA-NH2 to both mechanical and chemical noxious stimuli and i.t. TAPA-NH2 to mechanical noxious stimulus, i.t. TAPA-NH2-induced antinociception to chemical stimulus was significantly reduced by naloxonazine.