Forman Lloyd J
Department of Cell Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, 2 Medical Center Drive, Stratford, NJ 08084, USA.
Brain Res Bull. 2003 Jul 15;61(2):153-8. doi: 10.1016/s0361-9230(03)00103-5.
In the rat, antinociception of supraspinal origin is observed in response to administration of cocaine or an antagonist of the NMDA receptor for glutamate. The current study was conducted to determine if endocannabinoids are involved in the antinociceptive effect of cocaine, or antagonism of NMDA receptor binding. Intraperitoneal (i.p.) administration to male rats of cocaine, or the NMDA receptor antagonist, MK-801, resulted in a significant antinociceptive response of supraspinal origin, as indicated by a significant increase in reaction time in the hot plate test of analgesia (increase in the amount of time before the animal reacted to the hot plate by licking its paws or jumping). Treatment with SR141716A, a specific antagonist of the cannabinoid (CB1) receptor, resulted in a complete reversal of cocaine-induced antinociception when administered at a dose of 5.0mg/kg. Although the 2.5 and 5.0mg/kg doses of SR141716A produced a significant reduction in the antinociceptive effect of MK-801, the effect was incomplete since the reaction time in the hot plate test remained greater than that observed in vehicle-treated controls. These findings suggest that activation of the CB1 receptor participates significantly in antinociception resulting from treatment with cocaine and with the NMDA receptor antagonist, MK-801. The partial reversal of the antinociceptive effect of MK-801 by CB1 receptor antagonism indicates other mediators of nociception, in addition to the endocannabinoids, appear to be active in the antinociceptive response to NMDA receptor antagonism.
在大鼠中，观察到脊髓上起源的抗伤害感受是对可卡因或谷氨酸NMDA受体拮抗剂给药的反应。本研究旨在确定内源性大麻素是否参与可卡因的抗伤害感受作用或NMDA受体结合的拮抗作用。对雄性大鼠腹腔注射可卡因或NMDA受体拮抗剂MK-801，导致脊髓上起源的显著抗伤害感受反应，如热板镇痛试验中反应时间显著增加所示（动物通过舔爪或跳跃对热板做出反应之前的时间增加）。用大麻素（CB1）受体的特异性拮抗剂SR141716A以5.0mg/kg的剂量给药时，可完全逆转可卡因诱导的抗伤害感受。虽然2.5mg/kg和5.0mg/kg剂量的SR141716A显著降低了MK-801的抗伤害感受作用，但这种作用并不完全，因为热板试验中的反应时间仍大于溶剂处理对照组中观察到的反应时间。这些发现表明，CB1受体的激活在可卡因和NMDA受体拮抗剂MK-801治疗引起的抗伤害感受中起重要作用。CB1受体拮抗作用对MK-801抗伤害感受作用的部分逆转表明，除内源性大麻素外，其他伤害感受介质似乎在对NMDA受体拮抗作用的抗伤害感受反应中也有活性。
