SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism

Hong Yuan Chu, Qianqian Wu, Shanglin Zhou, Xiaohua Cao, Ao Zhang, Guo Zhang Jin, Guo Yuan Hu, Xuechu Zhen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 D1-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 D1 receptor antagonist SCH23390, the D2 receptor antagonist raclopride, the 5-HT2A/2C receptor antagonist mesulergine, or the α1-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 D1-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.

Original languageEnglish (US)
Pages (from-to)1259-1266
Number of pages8
JournalJournal of Neuroscience Research
Volume89
Issue number8
DOIs
StatePublished - Aug 1 2011

Keywords

  • Excitatory postsynaptic potential
  • Neuroprotection
  • Parkinson's disease
  • SKF83959
  • Voltage-gated Na channel

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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