The pharmacological activity of inhalation exposure to marijuana smoke in mice
The pharmacological activity of inhalation exposure to marijuana smoke in mice
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DOI：
10.1016/s0376-8716(00)00205-2
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发表时间：
2001-07-01
影响因子：
4.2
通讯作者：
Martin, BR
中科院分区：
文献类型：
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作者：
Lichtman, AH;Poklis, JL;Martin, BR
虽然大多数大麻素使用者吸食大麻，但实验动物研究的优势是通过注射Delta (9)-telrahydrocannabinol （Delta (9)-THC）或其他大麻素药物。本研究的目的是评估吸入大麻或乙醇提取的安慰剂烟雾对大麻素活性小鼠模型的影响，通过评估对自发活性、抗伤性、猝睡和体温的抑制。为了确定剂量学，在大麻暴露或静脉注射Delta (9)-THC后获得血液中Delta (9)-THC的水平。吸入大麻会产生与剂量相关的抗痛觉和麻痹性增加，估计Delta (9)-THC的ED50剂量分别为2.4和3.8 mg/kg。然而，暴露在安慰剂和大麻中的小鼠都出现了体温过低和运动抑制。CB1受体拮抗剂SR 141716A可拮抗大麻的抗伤感受作用（AD(50) = 0.6 mg/kg），但仅能轻微减轻大麻诱导的猝厥，且不能改变低体温或运动抑制效应。相比之下，SR 141716A在单独暴露于空气中的小鼠中拮抗静脉注射Delta (9)-THC的抗伤性、镇痛和降体温作用，尽管所有受试者都表现出运动抑制，这可能与抑制有关。根据其他人的报告，这些数据表明，仅接触烟雾就会产生药理学后果。我们的研究结果还表明，大麻诱导的抗痛觉是通过cb1受体的作用机制介导的，这与Delta (9)-THC主要负责这种作用的观点是一致的。(C) 2001爱思唯尔科学爱尔兰有限公司版权所有。
Although the majority of cannabinoid users smoke marijuana, the preponderance of laboratory animal research is based on administration of Delta (9)-telrahydrocannabinol (Delta (9)-THC) or other cannabinoid agents via injection. The aim of the present study was to evaluate the impact of inhaling marijuana, or ethanol-extracted placebo smoke in the mouse model of cannabinoid activity by assessing inhibition of spontaneous activity, antinociception, catalepsy, and body temperature. In order to determine dosimetry, blood levels of Delta (9)-THC were obtained following either marijuana exposure or intravenous injection of Delta (9)-THC. Inhalation exposure to marijuana produced dose-related increases in antinociception and catalepsy, with estimated ED50 doses of Delta (9)-THC of 2.4 and 3.8 mg/kg, respectively. However, hypothermia and locomotor depression occurred in both the placebo- and marijuana-exposed mice. The CB1 receptor antagonist, SR 141716A antagonized the antinociceptive effects of marijuana (AD(50) = 0.6 mg/kg), but only slightly decreased marijuana-induced catalepsy, and failed to alter either the hypothermic or locomotor depressive effects. In contrast, SR 141716A antagonized the antinociceptive, cataleptic, and hypothermic effects of intravenously administered Delta (9)-THC in mice that were exposed to air alone, though all subjects exhibited locomotor depression, possibly related to the restraint. In accordance with reports of others, these data suggest that exposure to smoke alone has pharmacological consequences. Our findings also indicate that marijuana-induced antinociception is mediated through a CB1-receptor mechanism of action and are consistent with the notion that Delta (9)-THC is mainly responsible for this effect. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.