Mechanisms for changes of endocannabinoid system in the brain

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Using various methods ranging from electrophysiology and molecular biology to behavioral testing with rodents and humans, we examined the interaction between stress and endocannabinoid system and their contributions to brain function. Our findings are as follows: (1) glucocorticoid-treatment increases neuronal excitability, and also decreases expression of CB1 cannabinoid receptors; (2) the endocannabinoid 2-AG has a CB1-independent excitatory action on neurons; (3) basal ganglia-dependent motor learning is impaired in CB1-knockout mice, and (4) learning strategy in probabilistic selection task depending on basal ganglia is altered in patients with mood disorders. These results are not inconsistent with the hypothesis that endocannabinoid system is involved in stress-induced alterations in brain function.