Differential effects of delta 9-THC on spatial reference and working memory in mice.
Differential effects of delta 9-THC on spatial reference and working memory in mice.
复制标题
Delta 9-THC 对小鼠空间参考和工作记忆的不同影响。
DOI：
10.1007/s002130100780
复制
发表时间：
2001
影响因子：
3.4
通讯作者：
Lichtman,AH
中科院分区：
文献类型：
--
作者：
Varvel,SA;Hamm,RJ;Martin,BR;Lichtman,AH
理由：在美国，大麻仍然是使用最广泛的非法药物，并且最近已经注意到大麻和大麻素衍生物的推定治疗用途。因此，更好地了解Δ9-THC（四氢大麻酚）诱导的记忆缺陷是至关重要的。这些实验旨在确定Δ9-THC是否对空间参考和工作记忆任务具有不同的作用，以研究其受体作用机制，并将这些效果与另外两种已知会导致记忆缺陷的化合物东莨菪碱和苯环己哌啶的效果进行比较。此外，Δ9-THC在这些记忆任务中的效力与其在传统上与cannabinoid activity.Methods相关的其他药理作用中的效力进行了比较：采用两种不同版本的Morris水迷宫：工作记忆任务和参考记忆任务。Δ9-THC的其他作用使用运动减退、抗伤害感受、僵住症和体温过低的标准测试进行评估。结果：Δ9-THC在低于破坏参考记忆任务的执行所需的剂量（100 mg/kg）的剂量下破坏工作记忆任务的执行（3.0 mg/kg），或引起运动减退、抗伤害感受、僵住症和体温过低。SR 141716 A逆转了这些性能缺陷。Δ9-THC的作用类似于东莨菪碱，东莨菪碱也选择性地破坏工作迷宫任务。相反，苯环利定破坏这两个任务，只有在剂量，也产生motor deficits.Conclusions：这些数据表明，Δ9-THC选择性地损害性能的工作记忆任务通过CB 1受体的作用机制，这些记忆中断是更敏感的比其他药理作用的Δ9-THC。
Rationale: Marijuana remains the most widely used illicit drug in the U.S., and recent attention has been given to putative therapeutic uses of marijuana and cannabinoid derivatives. Thus, developing a better understanding of Δ9-THC (tetrahydrocannabinol)-induced mnemonic deficits is of critical importance.Objectives: These experiments were conducted to determine whether Δ9-THC has differential effects on spatial reference and working memory tasks, to investigate its receptor mechanism of action, and to compare these effects with those produced by two other compounds – scopolamine and phencyclidine – known to produce mnemonic deficits. In addition, the potency of Δ9-THC in these memory tasks was compared with its potency in other pharmacological effects traditionally associated with cannabinoid activity.Methods: Two different versions of the Morris water maze were employed: a working memory task and a reference memory task. Other effects of Δ9-THC were assessed using standard tests of hypomotility, antinociception, catalepsy, and hypothermia.Results: Δ9-THC disrupted performance of the working memory task (3.0 mg/kg) at doses lower than those required to disrupt performance of the reference memory task (100 mg/kg), or elicit hypomotility, antinociception, catalepsy, and hypothermia. These performance deficits were reversed by SR 141716A. The effects of Δ9-THC resembled those of scopolamine, which also selectively disrupted the working maze task. Conversely, phencyclidine disrupted both tasks only at a dose that also produced motor deficits.Conclusions: These data indicate that Δ9-THC selectively impairs performance of a working memory task through a CB1receptor mechanism of action and that these memory disruptions are more sensitive than other pharmacological effects of Δ9-THC.