INTRODUCTION: The endocannabinoid system (ECS) is composed of cannabinoid (CB: CB1 and CB2) receptors and endocannabinoids, which are degraded by fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Thus, the function of the ECS might be modulated in a direct way, through CB receptor ligands or indirectly by FAAH and MAGL inhibitors. The ECS system is involved in many physiological functions, also through interaction with many systems. The cholinergic system plays a crucial role in memory processes. A connection with the ECS, especially CB and cholinergic receptor ligands, is supported by a large body of research. However, the influence of the ECS through an indirect manner in the context of cognitive processes remains poorly understood. AIM(S): The aim of the study was to evaluate the indirect influence of ECS, using of FAAH (URB 597) and MAGL (JZL 184) inhibitors, on memory related effects provoked by cholinergic receptor ligands, a cholinergic receptor agonist, nicotine, and a cholinergic receptor antagonist, scopolamine, in mice. METHOD(S): We assessed different memory stages using the passive avoidance (PA) test. A deficit in PA performance was expressed as the difference between retention and training latencies and is taken as an index of latency (IL). RESULTS: Co-administration of non-effective dose of JZL 184 (4 mg/kg), but not URB 597 (0.1 mg/kg), with a non‑effective dose of nicotine (0.05 mg/kg) enhanced both acquisition and consolidation of memory in the PA test in mice. An acute injection of JZL 184 (4 mg/kg) attenuated pro‑cognitive effects induced by effective dose of nicotine (0.1 mg/kg). In turn, co‑administration of URB (0.1 mg), but not JZL 184 (4 mg/kg), with scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice CONCLUSIONS: The present findings clearly indicate that the ECS, through an indirect manner, modulates memory processes, especially those in which cholinergic pathways are implicated.
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