Kurzfassung

In this project, we would like to focus on the role of endocannabinoids (EC) to counteract fear and anxiety, and to promote fear extinction. Studies indicate that the EC system is dynamically regulated during growth and differentiation of the CNS, but also in adulthood. First, we would like to investigate activity changes during normal or pathological aging. We will measure EC levels, quantify cannabinoid receptor activity, and EC synthesising and degrading enzymes in several brain regions...In this project, we would like to focus on the role of endocannabinoids (EC) to counteract fear and anxiety, and to promote fear extinction. Studies indicate that the EC system is dynamically regulated during growth and differentiation of the CNS, but also in adulthood. First, we would like to investigate activity changes during normal or pathological aging. We will measure EC levels, quantify cannabinoid receptor activity, and EC synthesising and degrading enzymes in several brain regions that are involved in learning and memory, anxiety and stress responses, both in young, middle aged and old wild-type mice as well as in a mouse model of Alzheimer disease. Next, EC-mediated fear extinction, EC system dynamics, and EC-dependent synaptic transmission in amygdala and hippocampus will be determined in wild-type mice of different age. Age-dependence in EC-mediated fear extinction will be investigated in various neuron-specific CB1 receptor-deficient mice. Finally, we aim at enhancing the anxiolytic and extinction-promoting effects of CB1 receptor activation by pharmacological, dietary, and genetic means. As dysregulated fear reaction and extinction are distinctive features of posttraumatic stress disorder, panic attacks or phobias, a detailed understanding of the EC system dynamics will open new therapeutic avenues.» weiterlesen» einklappen