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SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor‐independent mechanism
Author(s) -
Chu HongYuan,
Wu Qianqian,
Zhou Shanglin,
Cao Xiaohua,
Zhang Ao,
Jin GuoZhang,
Hu GuoYuan,
Zhen Xuechu
Publication year - 2011
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22653
Subject(s) - excitatory postsynaptic potential , neurotransmission , neuroscience , chemistry , biology , inhibitory postsynaptic potential , receptor , biochemistry
Abstract Dopamine (DA) profoundly modulates excitatory synaptic transmission and synaptic plasticity in the brain. In the present study the effects of SKF83959, the selective agonist of phosphatidylinositol (PI)‐linked D 1 ‐like receptor, on the excitatory synaptic transmission were investigated in rat hippocampus. SKF83959 (10–100 μM) reversibly suppressed the field excitatory postsynaptic potential (fEPSP) elicited by stimulating the Schaffer's collateral‐commissural fibers in CA1 area of hippocampal slices. However, the inhibition was not blocked by the D 1 receptor antagonist SCH23390, the D 2 receptor antagonist raclopride, the 5‐HT 2A/2C receptor antagonist mesulergine, or the α 1 ‐adrenoceptor antagonist prazosin. In addition, SKF83959 inhibited the afferent volley and significantly reduced the paired‐pulse facilitation ratios. In dissociated hippocampal CA1 pyramidal neurons, SKF83959 had no detectable effect on glutamate‐induced currents but potently inhibited voltage‐activated Na + current (IC50 value = 26.9 ± 1.0 μM), which was not blocked by SCH23390 or by intracellular dialysis of GDP‐β‐S. These results demonstrate that SKF83959 suppressed the excitatory synaptic transmission in hippocampal CA1 area, which was independent of D 1 ‐like receptor. The mechanism underlying the effect could be mainly inhibition of Na + channel in the afferent fibers. The suppression of excitatory synaptic transmission and the Na + channel by SKF83959 may contribute to its therapeutic benefits in Parkinson's disease. © 2011 Wiley‐Liss, Inc.