Delta(9)-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism
Delta(9)-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism
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DOI：
10.1007/bf02246347
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发表时间：
1996-07-01
影响因子：
3.4
通讯作者：
Martin, BR
中科院分区：
文献类型：
--
作者：
Lichtman, AH;Martin, BR
本研究的目的是探讨大麻素和胆碱能系统是否通过共同的机制损害工作记忆。通过检查大麻素拮抗剂SR 141716 A是否会改善由天然存在的大麻素、δ（9）-THC或东莨菪碱（一种毒蕈碱拮抗剂）引起的桡臂性能缺陷来检验该假设。此外，我们评估了胆碱酯酶抑制剂毒扁豆碱是否能预防Delta（9）-THC诱导的空间记忆障碍。最后，由于大麻素的运动抑制作用可能会降低桡臂选择的准确性，而不依赖于对记忆的直接影响，因此我们研究了增加试验间误差对桡臂选择准确性的影响。如先前报道的，Delta（9）-THC损害迷宫表现（艾德（50）=3.0 mg/kg）。将试验间隔从5秒增加到30秒导致完成迷宫所需的时间增加了三倍，而不影响选择的准确性。重要的是，SR 141716 A以剂量依赖性方式（AD（50）=2.4 mg/kg）预防Delta（9）-THC诱导的桡侧臂选择准确性缺陷;然而，大麻素拮抗剂未能改善东莨菪碱的破坏性作用。相反，毒扁豆碱未能改善Delta（9）-THC产生的性能缺陷。这些数据提供了有力的证据，证明Delta（9）-THC通过直接作用于大麻素受体而损害工作记忆。此外，这些结果表明，东莨菪碱和Delta（9）-THC不会损害共同串行通路中的空间记忆，尽管它们可能会集中在第三个神经化学系统。
The purpose of the present study was to investigate whether the cannabinoid and cholinergic systems impair working memory through a common mechanism. This hypothesis was tested by examining whether the cannabinoid antagonist SR141716A would ameliorate radial-arm performance deficits caused by either the naturally occurring cannabinoid, Delta(9)-THC, or scopolamine, a muscarinic antagonist. In addition, we evaluated whether the cholinesterase inhibitor, physostigmine, would prevent Delta(9)-THC-induced impairment of spatial memory. Finally, because the locomotor suppressive effects of cannabinoids may decrease radial arm choice accuracy independent of a direct effect on memory, we examined the impact of increasing the intertrial error on radial arm choice accuracy. As previously reported, Delta(9)-THC impaired maze performance (ED(50)=3.0 mg/kg). Increasing the intertrial interval from 5 s to 30 s resulted in a three-fold increase in the amount of time required to complete the maze without affecting choice accuracy. Importantly, SR141716A prevented Delta(9)-THC-induced deficits in radial-arm choice accuracy in a dose-dependent manner (AD(50)=2.4 mg/kg); however, the cannabinoid antagonist failed to improve the disruptive effects of scopolamine. Conversely, physostigmine failed to improve performance deficits produced by Delta(9)-THC. These data provide strong evidence that Delta(9)-THC impairs working memory through direct action at cannabinoid receptors. Moreover, these results suggest that scopolamine and Delta(9)-THC do not impair spatial memory in a common serial pathway, though they may converge on a third neurochemical system.