Involvement of the endocannabinoid system in posttraumatic stress disorder
Posttraumatic stress disorder (PTSD) belongs to the most frequent anxiety disorders. It develops in the aftermath of a traumatic life event and represents a clear public health problem. In spite of its increasing incidence, there...
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Descripción del proyecto
Posttraumatic stress disorder (PTSD) belongs to the most frequent anxiety disorders. It develops in the aftermath of a traumatic life event and represents a clear public health problem. In spite of its increasing incidence, there are no established effective treatments for this disorder. In addition, even though a broad body of evidence concerning neurobiological correlates of this illness, the pathomechanisms of PTSD is still poorly understood. Therefore, there is a need to identify new therapeutic targets/strategies for PTSD. Interestingly, only 10-15 percent of the people confronted with a trauma develop PTSD in its aftermath. This points to the existence of highly efficient salutogenic (i.e. health promoting) factors. With the help of animal models we have accumulated preliminary evidence that the endocannabinoid system of the brain plays an important role in the modulation of processes occurring in PSTD and is pointed out as a potential therapeutic target for this neuropsychiatric disorder. The involvement of ECS in the development of PTSD symptoms seems to critically depend on the neuronal population affected. For instance, CB1 on glutamatergic neurons constrain the expression of fear responses, once the averseness of the test situation has surpassed a certain threshold. Therefore, the general objective of this research proposal is to unravel the time point, sites and consequences of attenuated CB1 buffered glutamate signalling in a mouse model of PTSD. To address this issue, we will combine genetic, in vivo imaging, electrophysiology, behavioural and biochemical studies in mice. The achievement of these objectives will provide new insights into the mechanisms underling the involvement of endocannabinoid system into the adverse consequences of a traumatic experience that might lead to the development of new therapeutic approaches for the treatment of PTSD that are based on downscaling glutamate release at presynaptic terminals.