The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by Δ9-tetrahydrocannabinol or anandamide
The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by Δ9-tetrahydrocannabinol or anandamide
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DOI：
10.1007/s002130050733
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发表时间：
1998-11-01
影响因子：
3.4
通讯作者：
Beninger, RJ
中科院分区：
文献类型：
--
作者：
Mallet, PE;Beninger, RJ
δ（9）-四氢大麻酚（THC），大麻中的主要精神活性成分，或内源性大麻素anandamide的管理，已被证明会损害最近的记忆。本研究的目的是确定大麻素CBI受体拮抗剂SR 141716 A是否可以减轻THC或anandamide诱导的记忆障碍，并评估SR 141716 A单独对记忆的影响。记忆进行了评估，在大鼠训练有素的两个组成部分的工具歧视任务，包括条件歧视，和非匹配的位置，以评估最近或工作记忆。SR 141716 A（0.0-2.0 mg/kg）对条件性辨别或非匹配位置均无影响。然而，SR 141716 A（0.0-2.0 mg/kg）减轻了THC（2.0或4.0 mg/kg）产生的记忆障碍，表现为非匹配位置的表现增强。当给予用大麻素（2.0 mg/kg）预处理的大鼠时，SR 141716 A（0.0-2.5 mg/kg）在最高剂量下损害了条件性辨别的表现。这被解释为与记忆无关的某些能力的缺陷（例如，运动障碍）。然而，较低剂量的SR 141716 A（0.1和0.5 mg/kg）减弱了anandamide诱导的非匹配位置性能损害，而不影响条件性辨别。这是第一份报告，大麻素拮抗剂可以减弱anandamide产生的记忆障碍;结果表明，anandamide诱导的记忆破坏是由CB 1受体介导的。
The administration of Delta(9)-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana, or the endogenous cannabinoid anandamide, has been shown to impair recent memory. The purpose of the present investigation was to determine if the cannabinoid CBI receptor antagonist SR141716A could attenuate THC- or anandamide-induced memory impairment, and to assess the effects on memory of SR141716A alone. Memory was assessed in rats well-trained in a two-component instrumental discrimination task, consisting of a conditional discrimination, and a non-match-to-position to assess recent or working memory. SR141716A (0.0-2.0 mg/kg) had no effect on either the conditional discrimination or the non-match-to-position. However, SR141716A (0.0-2.0 mg/kg) attenuated the memory impairment produced by THC (2.0 or 4.0 mg/kg) as indexed by an enhancement of performance in the non-match-to-position. When administered to rats pretreated with anandamide (2.0 mg/kg), SR141716A (0.0-2.5 mg/kg) impaired performance in the conditional discrimination at the highest dose. This was interpreted as a deficit in some capacity unrelated to memory (e.g., motor impairment). However, lower doses of SR141716A (0.1 and 0.5 mg/kg) attenuated the anandamide-induced impairment of performance in the non-match-to-position without affecting the conditional discrimination. This is the first report that the memory impairment produced by anandamide can be attenuated by a cannabinoid antagonist; results suggest that anandamide-induced memory disruption is mediated by CB1 receptors.