Endocannabinoids (eCBs) are involved in the hippocampal mechanisms of spatial learning and memory in rats. Although eCBs exert many of their actions on spatial learning and memory via CB1 receptors, the putative cannabinoid receptor GPR55 (expressed in the hippocampus, cortex, forebrain, cerebellum and striatum) seems to be also involved. To investigate the potential role of GPR55 in spatial learning and memory, Wistar rats received bilateral infusions of lysophosphatidylinositol (LPI, GPR55-agonist) into the hippocampus 5-minutes before training-phase in the Barnes-maze (BM). This manipulation increased the use of serial navigation while preventing the learning of spatial navigation strategy and decreasing the use of random activity to find the escape-tunnel in the BM. In contrast, CID16020046 (GPR55-antagonist) increased the use of random activity at the expense of spatial and serial navigation strategies. Finally, CID16020046 significantly reduced the time spent in the target zone during a retention test. Our results suggest: (i) a potential role of GPR55 in developing navigation strategies; (ii) a prospective function for LPI acting in hippocampal CA1 (probably via GPR55) to perform a serial navigation strategy; and (iii) a potential role of GPR55 in the mechanisms involved in spatial memory (object placement memory).
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