JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects.
JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects.
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DOI：
10.1016/j.ejphar.2014.06.023
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发表时间：
2014-10-05
影响因子：
5
通讯作者：
McMahon, Lance R.
中科院分区：
文献类型：
--
作者：
Rodriguez, Jesse S.;McMahon, Lance R.
比较了滥用合成大麻素JWH-018和Δ-9-四氢大麻酚(Δ-9-THC)对恒河猴的几种作用。JWH-018(0.1 mg/kg静脉注射)被确定为歧视性刺激，利莫那班被用来检查导致歧视的机制以及操作反应、减速和低温效应。JWH-018呈剂量依赖性增加药效(ED50=0.01 mg/kg)和降低应答率(ED50=0.064 mg/kg)。在不同的大麻素中，产生辨别性刺激和减速作用的相对效力是相同的：CP-55940=JWH-018>；Δ9-THc=Win-55212-2=JWH-073。苯二氮卓类激动剂咪达唑仑和NMDA拮抗剂氯胺酮在干扰反应的剂量下没有发挥JWH-018那样的辨别性刺激效应。JWH-018和9-THC使直肠温度分别降低2.2℃和2.8℃，降低2℃的剂量分别为0.21 mg/kg和1.14 mg/kg。JWH-018和9-THC的拮抗作用无差异，但作用不同。在JWH-018和Δ-9-THC存在下计算的利莫那班对区分刺激效应的拮抗作用(分别为6.58和6.59)和低温效应的表观亲和力(分别为7.08和7.19)没有差别。表观亲和力估计与介导JWH-018和Δ9-THC的区别性刺激和低温效应的相同受体一致。然而，降速效应的拮抗作用更为有限和有序，这表明大麻素对应答率的影响可能涉及另一种受体机制。总体而言，这些结果强烈表明，JWH-018和Δ9-THC作用于相同的受体，产生几种共同的精神药理作用。
Several effects of the abused synthetic cannabinoid JWH-018 were compared to those of Δ9-tetrahydrocannabinol (Δ9-THC) in rhesus monkeys. JWH-018 (0.1 mg/kg i.v.) was established as a discriminative stimulus and rimonabant was used to examine mechanisms responsible for discrimination as well as operant response rate-decreasing and hypothermic effects. JWH-018 dose-dependently increased drug-lever responding (ED50 = 0.01 mg/kg) and decreased response rate (ED50 = 0.064 mg/kg). Among various cannabinoids, the relative potency for producing discriminative stimulus and rate-decreasing effects was the same: CP-55940 = JWH-018 > Δ9-THC = WIN-55212-2 = JWH-073. The benzodiazepine agonist midazolam and the NMDA antagonist ketamine did not exert JWH-018 like discriminative stimulus effects up to doses that disrupted responding. JWH-018 and 9-THC decreased rectal temperature by 2.2 and 2.8 °C, respectively; the doses decreasing temperature by 2 °C were 0.21 and 1.14 mg/kg, respectively. Antagonism did not differ between JWH-018 and 9-THC, but did differ among effects. The apparent affinities of rimonabant calculated in the presence of JWH-018 and Δ9-THC were not different from each other for antagonism of discriminative stimulus effects (6.58 and 6.59, respectively) or hypothermic effects (7.08 and 7.19, respectively). Apparent affinity estimates are consistent with the same receptors mediating the discriminative stimulus and hypothermic effects of both JWH-018 and Δ9-THC. However, there was more limited and less orderly antagonism of rate-decreasing effects, suggesting that an additional receptor mechanism is involved in mediating the effects of cannabinoid on response rate. Overall, these results strongly suggest that JWH-018 and Δ9-THC act at the same receptors to produce several of their shared psychopharmacological effects.
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影响因子：
4.1
作者：
Pertwee RG
通讯作者：
Pertwee RG
影响因子：
3.5
作者：
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影响因子：
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作者：
McMahon LR
通讯作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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