Synergistic but not additive effect between ACPA and lithium in the dorsal hippocampal region on spatial learning and memory in rats: Isobolographic analyses

Abstract

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.