CB1 Receptor Involved in the Impairment of Exercise-induced Fatigue on Corticostriatal eCB-LTD

Objective: The aim of the present study is to investigate the effect of exercise-induced fatigue on corticostriatal synaptic plasticity by observing the changes of endocannabinoid-mediated long-term depression (e CB-LTD) after exercise-induced fatigue. Methods: Adult male C57 BL/6 mice were randomly divided into two groups: control mice and exercise-induced fatigue (EF) mice. Electric treadmill was used to establish a repetitive exhausted EF mouse model. The corticostriatal LTD of two groups were examined by using in vitro field excitatory postsynaptic potential (f EPSP) recording technique. And the CB1 receptor antagonist AM251 was applied to examine whether this corticostriatal LTD was e CB-dependent. In vitrowhole-cell patch clamp recording was used to detect the basic electrophysiological properties of medium spiny neurons (MSNs) . Western blotting was used to examine the expression of CB1 receptor in the striatum. Results: 1) The corticostriatal LTD in EF mice was significantly impaired compared with the control group (P < 0.01) , and the LTD was blocked by CB1 receptor antagonist AM251, thus it was eCB-LTD. 2) The basic electrophysiological properties of MSNs in EF mice were normal (P>0.05) . 3) Compared with the control group, the striatal expression of CB1 receptor in EF mice was significantly increased (P<0.01) . Conclusion: The corticostriatal eCB-LTD was impaired in EF mice, but the basic electrophysiological properties of MSNs were normal, whereas the elevated CB1 receptor expression may be a compensatory response to the e CB-LTD deficit. Our results demonstrate that EF impairs the corticostriatal e CB-LTD for the first time, and suggest that the aberrant corticostriatal synaptic plasticity may be involved in the production and/or maintenance of EF.