期刊
NEUROPHARMACOLOGY
卷 57, 期 2, 页码 164-171出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.05.001
关键词
SKF83959; Dopamine receptor; Hippocampus; LTD; Field EPSPs; Calcium
资金
- National Basic Research Program of China [2007CB507404]
- Chang Jiang Scholar Program
- Ph.D. Program Foundation [20060487020]
- Ministry of Education of China
- NSFC [30600658]
- Program for New Century Excellent Talents in Universities of China
Recent work has demonstrated that a phosphatidylinositol (PI)-linked D-1 dopamine receptor selective agonist, SKF83959, mediates phosphatidylinositol hydrolysis via activation of phospholipase C in brain. Specific contributions of SKF83959 to synaptic plasticity have not been well elucidated. The aim of the current investigation was to characterize the role of SKF83959 on long-term depression (LTD) in the CA1 region of rat hippocampal slices and to explore the molecular events leading to these changes. The results indicated that SKF83959 stimulation significantly depressed field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner and facilitated the induction of LTD by LFS. SKF83959-facilitated LTD required activation of phospholipase C (PLC). NMDA receptors were involved in this response. Calcium chelator, BAPTA-AM prevented SKF83959-facilitated LTD, indicating that cytosolic free calcium concentration ([Ca2+](i)) elevation could account for this response. Furthermore, SKF83959-facilitated LTD was significantly depressed in the presence of calcineurin (PP2B) inhibitors cyclosporin A (CsA) and associated with a persistent increase in the expression of calcineurin A. Taken together, these findings demonstrate a novel role for PI-linked D, dopamine receptor in the neuromodulation of hippocampal LTD. (C) 2009 Elsevier Ltd. All rights reserved.
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