Smith F L, Cichewicz D, Martin Z L, Welch S P
Department of Pharmacology and Toxicology, Medical College of Virginia, Richmond 23298-0613, USA.
Pharmacol Biochem Behav. 1998 Jun;60(2):559-66. doi: 10.1016/s0091-3057(98)00012-4.
We have previously reported that intracerebroventricular or intrathecal administration of inactive doses of delta9-tetrahydrocannabinol (THC) greatly enhance the antinociceptive potency of morphine in the mouse tail-flick test. Experiments were conducted to test the hypothesis that morphine's potency would be enhanced in mice receiving THC and morphine by conventional per os (p.o.) and subcutaneously (s.c.) routes of administration. Antinociception was measured in the tail-flick test of radiant heat after administration of different combinations of THC and morphine p.o. and s.c. Subcutaneous administration of THC (4 and 25 mg/kg) increased the potency of s.c. morphine 8.5- and 22.3-fold, respectively, while s.c. THC (25 mg/kg) increased the potency of p.o. morphine 3.1-fold. Per os administration of THC (10 and 20 mg/kg) increased the potency of s.c. and p.o. morphine 11.4-fold and 7.6-fold, respectively. Thus, morphine's potency was significantly increased regardless of the enteral and parenteral routes of THC and morphine administration. The synthetic receptor selective cannabinoid CP-55, 940 (0.1 mg/kg, s.c.) also enhanced morphine's potency. Finally, the ability of the CB1 receptor antagonist SR141716A to antagonize the enhancement of morphine by THC indicates that THC was acting through a cannabinoid receptor mechanism.
我们之前曾报道，在小鼠甩尾试验中，脑室内或鞘内注射无活性剂量的Δ9-四氢大麻酚（THC）可显著增强吗啡的镇痛效力。本实验旨在验证以下假设：通过传统的口服（p.o.）和皮下（s.c.）给药途径给予THC和吗啡的小鼠，吗啡的效力会增强。在口服和皮下给予不同组合的THC和吗啡后，通过辐射热甩尾试验测量镇痛效果。皮下注射THC（4和25mg/kg）分别使皮下注射吗啡的效力提高了8.5倍和22.3倍，而皮下注射THC（25mg/kg）使口服吗啡的效力提高了3.1倍。口服THC（10和20mg/kg）分别使皮下和口服吗啡的效力提高了11.4倍和7.6倍。因此，无论THC和吗啡是通过肠内还是肠外途径给药，吗啡的效力均显著提高。合成受体选择性大麻素CP-55,940（0.1mg/kg，皮下注射）也增强了吗啡的效力。最后，CB1受体拮抗剂SR141716A拮抗THC对吗啡增强作用的能力表明，THC是通过大麻素受体机制发挥作用的。
