SYSTEMIC OR INTRAHIPPOCAMPAL CANNABINOID ADMINISTRATION IMPAIRS SPATIAL MEMORY IN RATS
SYSTEMIC OR INTRAHIPPOCAMPAL CANNABINOID ADMINISTRATION IMPAIRS SPATIAL MEMORY IN RATS
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DOI：
10.1007/bf02246292
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发表时间：
1995-06-01
影响因子：
3.4
通讯作者：
MARTIN, BR
中科院分区：
文献类型：
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作者：
LICHTMAN, AH;DIMEN, KR;MARTIN, BR
本研究的目的是调查大麻素对工作记忆的破坏性影响，在八臂径向迷宫中进行评估。全身给予Delta（9）-THC、WIN-55，212 -2和CP-55，940增加了径向迷宫中的错误数量。CP-55，940是损害记忆力最有效的大麻素（艾德（50）= 0.13 mg/kg）。Δ（9）-THC和WIN-55，212 -2在等效剂量（艾德（50）值分别= 2.1和2.2 mg/kg）下破坏迷宫选择准确性。此外，这些药物的全身给药延迟了完成时间。尽管延迟迷宫表现所需的Delta（9）-THC和CP-55，940的剂量高于增加错误数所需的剂量，但WIN-55，212 -2在这两种测量中是等效的。另一方面，无论是花生四烯酸，假定的内源性大麻素配体，也不是大麻二酚，一种无活性的天然大麻素，对记忆有任何明显的影响。本研究的第二个目的是阐明介导大麻素对记忆的破坏性影响的神经解剖学底物。海马内注射CP-55，940以剂量依赖性方式损害迷宫表现（艾德（50）= 8 μ g/大鼠），但不延迟完成迷宫所需的时间。海马内CP-55，940的作用显然对认知是特异性的，因为没有其他大麻素药理学作用（例如，抗伤害感受、体温过低和僵住症）。在径向迷宫中的选择准确性和其他大麻素药理学作用之间的这种分离表明，大麻素产生的工作记忆缺陷可能是由海马中的大麻素受体介导的。
The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of Delta(9)-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED(50) = 0.13 mg/kg). Delta(9)-THC and WIN-55,212-2 disrupted maze-choice accuracy at equipotent doses (ED(50) values = 2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of Delta(9)-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED(50) = 8 mu g/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.