Lithium and cannabinoids can disrupt learning and memory performance. The goal of the present study is to investigate the additive or synergistic effect of lithium and cannabinoid combination doses on spatial learning and memory in rats by isobolographic analyses. Although several studies have suggested synergistic effects of cannabinoids or lithium in response to other compounds, in most of them isobolographic analyses were not used; Thus, there is a need for more detailed studies using isobolographic analyses. In this study, spatial memory was evaluated in the Morris Water Maze (MWM) apparatus by eight trials in the training day and one trial in the test day. Lithium was injected intraperitoneal and ACPA (cannabinoid type 1 receptor agonist) was injected into the dorsal hippocampal region (intra-CA1). For the isobolographic analyses, the ED50 of lithium (2.5 mg/kg) and ACPA (0.5 μg/rat) was measured by linear regression analysis, considering the doses were tested in our previous research. The results showed that, combinations of low, medium and high doses of lithium (0.312 mg/kg, 0.625 mg/kg and 1.25 mg/kg, respectively) and ACPA (0.0625 μg/rat, 0.125 μg/rat and 0.25 μg/rat, respectively) had synergistic but not additive effect on spatial learning and spatial memory. In conclusion, we suggest that combination doses of lithium and ACPA have synergistic but not additive effect on spatial learning and memory in the rat's dorsal hippocampal region.

中文翻译：

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ACPA和背海马区锂对大鼠空间学习和记忆的协同作用但不是累加作用：等效线描图分析。

锂和大麻素会破坏学习和记忆性能。本研究的目的是通过等效线描法分析研究锂和大麻素联合剂量对大鼠空间学习和记忆的累加或协同作用。尽管有几项研究表明大麻素或锂对其他化合物具有协同作用，但在大多数研究中并未使用等效线描记法分析。因此，需要使用等效线描记分析进行更详细的研究。在这项研究中，通过在训练日进行八项试验，在测试日进行一项试验，在莫里斯水迷宫（MWM）装置中评估了空间记忆。腹膜内注射锂，ACPA（大麻素1型受体激动剂）注射至背侧海马区（CA1内）。对于等效线描记法分析，考虑到在我们先前的研究中已经测试了剂量，通过线性回归分析测量了锂（2.5 mg / kg）和ACPA（0.5μg/大鼠）的ED50。结果表明，低，中和高剂量锂（分别为0.312 mg / kg，0.625 mg / kg和1.25 mg / kg）和ACPA（0.0625μg/ rat，0.125μg/ rat和0.25μg/ rat）的组合分别对空间学习和空间记忆具有协同作用，但没有相加作用。总之，我们建议锂和ACPA的联合剂量对大鼠背侧海马区的空间学习和记忆具有协同作用，但没有累加作用。分别为312 mg / kg，0.625 mg / kg和1.25 mg / kg）和ACPA（分别为0.0625μg/只，0.125μg/只和0.25μg/只）对空间学习和空间记忆具有协同作用，但没有累加作用。总之，我们建议锂和ACPA的联合剂量对大鼠背侧海马区的空间学习和记忆具有协同作用，但没有累加作用。分别为312 mg / kg，0.625 mg / kg和1.25 mg / kg）和ACPA（分别为0.0625μg/只，0.125μg/只和0.25μg/只）对空间学习和空间记忆具有协同作用，但没有累加作用。总之，我们建议锂和ACPA的联合剂量对大鼠背侧海马区的空间学习和记忆具有协同作用，但没有累加作用。