Role Of CB1 Receptor In Spatial Reference Memory Impairment Induced By Stress In Mice

Stress affects the brain mechanisms of learning and memory, which is the focus of the present neurophysiology study. Stress has a significant influence on learning and memory function. The initial studies have shown that the amount of studies investigating the mechanism of the physiological function of stress in learning and memory has dramatically increased, and many effects of stress interact with some neurotransmitter. Moreover, a number of neuropeptides in the brain are involved in the stress-induced cognitive dysfunction. Since the discovery of endocannabinoid system, researchers increasingly recognize that it plays a important role in the brain. It has been found that there are cannabinoid Ⅰ (CB1) and Ⅱ(CB2) receptors at least, normally, CB1 receptors major distributed in the brain and spinal cord, CB2 receptors distributed in the peripheral nervous system. Numerous studies show that:owe to CB1 receptors are widespread throughout the brain, the researchers found that they involved in the regulation of the cognitive process of animal and human. cognition is a process of information processing for animals, which includes the person’s feeling, perception, memory, thinking and imagination. we mainly study the learning and memory, and it can be divided into three stages of acquisition, consolidation, retrieval. Current research on learning and memory in neurophysiology focused on the mechanisms of memory formation, and the formation mechanism of working memory and spatial reference memory is also different. Current research shows that cannabinoid system has different effects on learning and memory, and its mechanism of action is not clear. But it was discovered that CB1 receptor could inhibit the hypothalamic-pituitary-adrenal axis (HPA axis) under stress conditions, and activation of the HPA axis could affect learning and memory, so what role the CB1 receptors plays in the damage of spatial reference learning and memory caused by stress is a worthy scientific questions.In this study, we investigate the effects of the elevated platform stress on the spatial reference memory in the Morris water maze in mice, and study the effects of CB1 receptors in learning and memory disorders caused by the stress. It provide valuable clues to explore the effects of cannabinoid on the mechanisms of learning and memory. It contains:(1) the effect of cannabinoid CB1 receptor antagonist AM281 (3mg/kg) on the acquisition, consolidation and retrieval of spatial reference memory; (2) the function of cannabinoid CB1 receptor antagonist AM281 (3mg/kg) on the impairment of reference memory caused by the elevated platform stress in mice.In this study, (1) CB1 receptor antagonist AM281 administration (i.p.) respectively inhibit the CB1 receptors in the stage of acquisition, consolidation, retrieval in Morris water maze in mice, we obtain that it has no effect on space reference memory in mice; (2) We establish the model of the elevated platform stress before training, after training and before the test in Morris water maze, and then administration (i.p.) of CB1 receptor antagonist AM281 inhibit the CB1 receptors, and observing the changes of spatial reference learning and memory in mice. We find that the acquisition and retrieval of spatial reference learning and memory will be damaged if mice was given the elevated platform stress before training, this damage can be reversed if CB1 receptors is suppressed after the stress; the retrieval of spatial reference learning and memory will be damaged if mice was given the elevated platform stress after training and before the test, and this damage can be reversed if CB1 receptors is suppressed after the stress.The study show that CB1 receptors involved in the damage of spatial reference learning and memory caused by stress, the activation of CB1 receptor may mediate the process of the damage of learning and memory caused by acute stress. It also influenced by many factors, such as:CB1 receptors antagonist administration (i.p.) before or after the elevated platform stress, before training, after training, before the test, these may produce different effects. So it also need some further considerations to obtain the mechanism of CB1 receptors involved in the damage of learning and memory caused by stress.