Inhibition Of The Effects Of Endogenous Cannabinoid 2-AG Synthesis On Learning Memory And Mood

Endocannabinoid system is a lipid signaling system that participates in mediating stress,learning,memory,pain and mood and other physiological functions.Growing evidence indicates that the endocannabinoid system is important for learning and memory.Learning and memory helps organisms to predict and adapt to events in environment.Gained experience leaves traces of memory in the nervous system.Yet,memory formation in vertebrates and invertebrates is a highly complex and dynamic process that consists of different phases,which depend on various neuronal and molecular mechanisms.Endocannabinoid system is not only related to learning and memory,but also has an effect on emotions.It has been found that disturbing endocannabinoid system can cause anxiety.2-arachidonoylglycerol(2-AG)is a major endocannabinoid in organisms,which role in memory and emotion is still not clear.This study investigates the role of 2-AG in emotion,learning and memory by inhibiting the synthesis enzyme diacylglycerol lipase a(DAGL-a).In order to elucidate the physiological effects of 2-AG in behavioral and cognitive functions,it is important to inhibit 2-AG major synthetase DAGL.Firstly,we used DAGL-a knock-out mice for comprehensive behavioral test.The learning and memory of DAGL KO mice were tested by using three behavioral paradigms,including new object recognition,context freezing coditioning and Morris water maze experiments.Also a 30 min open field experiment and a 10 min elevated cross maze were also performed for anxiety-realted emotional test.Secondly,injecting Orlistat on hippocampus to explore its effects on the animal memory retrieval during context freezing coditioning and new object recognition memory tasks,as well as the anxiety-realted behavioral phenotypes in the open field and elevated cross maze.The result is 1.DAGL-a KO mice showed normal spatial reference learning and memory in the MWM experiment,however,he learning and memory of DAGL KO mice were enhanced in contextual fear memory test and in new object recognition tests.Therefore,learning-memory change in DAGL-a KO mice are task-dependent..Anxiety level of DAGL-a KO mice was higher than that of the control group at 10～20 min and 20～30 min during the 30 min open field experiment,in the elevated cross maze task,however,no difference was observed between DAGL-a KO and control mice.2.Microinjection of Orlistat showed no effect on the memory retrieval stage in contextual fear memory experiment and the new object recognition experiment.The anxiety level of the hippocampus 2μg Orlistat injected mice was significantly decrease than the 1μg Orlistat group and Vehicle control group.Our results suggest that hippocampal injection of Orlistat reduced anxiety,but did not contribute to the contextual fear memory retrieval and new object recognition memory retrieval.Knock-outing Dagla gene enhanced anxiety-like reactions and improved contextual fear memory and new object recognition memory.Therefore,inhibiting the synthesis of 2-AG can improve the learning and memory of animals,affecting the emotion of animals,but the regulation of emotion is still inconclusive.