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OBJECTIVE AQP4 is widely expressed in brain astrocytes,and its function is mainly to maintain the steady-state of brain water.D-serine as an important neurotransmitter secreted by glial cells is an endogenous co-agonist of NMDA receptor,and is essential for the induction of long-term potentiation.The present study is to explore whether D-serine is mediated the change of synaptic plasticity and cocaine-induced addictive behavior induced by AQP4 knockout.METHODS The effects of D-serine on NAc LTD and behavior of AQP4 knockout mice were investigated by electrophysiological recording and behavioral tests.RESULTS 10 μmol·L-1 D-serine significantly reversed NMDA receptor-dependent LTD in AQP4 KO mice NAc slices.D-serine concentration-dependently antagonized the effects of AQP4 knockout on cocaine addiction behavior.500 mg·kg-1 D-serine significantly increased cocaine-induced locomotor activity in AQP4 KO mice.D-serine(500 mg·kg-1) significantly restored cocaine-induced conditioned place preferences in AQP4 KO mice.CONCLUSION AQP4 knockout changed the behavior of cocaine addiction through affecting the release of D-serine in glial cells.
OBJECTIVE AQP4 is widely expressed in brain astrocytes, and its function is mainly to maintain the steady-state of brain water. D-serine as an important neurotransmitter secreted by glial cells is an endogenous co-agonist of NMDA receptor, and is essential for the induction of long-term potentiation. The present study is to explore whether D-serine is mediated the change of synaptic plasticity and cocaine-induced addictive behavior induced by AQP4 knockout. METHODS The effects of D-serine on NAc LTD and behavior of AQP4 knockout mice were investigated by electrophysiological recording and behavioral tests .RESULTS 10 μmol·L-1 D-serine like mutated NMDA receptor-dependent LTD in AQP4 KO mice NAc slices. D-serine concentration-dependently antagonized the effects of AQP4 knockout on cocaine addiction behavior D-serine significantly increased cocaine-induced locomotor activity in AQP4 KO mice. D-serine (500 mg · kg -1) significantly restored cocaine-induced conditioned place preferences in AQP4 KO mice. CONCLUSION AQP4 knockout changed the behavior of cocaine addiction through affecting the release of D-serine in glial cells.