SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism
✍ Scribed by Hong-Yuan Chu; Qianqian Wu; Shanglin Zhou; Xiaohua Cao; Ao Zhang; Guo-Zhang Jin; Guo-Yuan Hu; Xuechu Zhen
- Book ID
- 102384686
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 499 KB
- Volume
- 89
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
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 lM) 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 a 1 -adrenoceptor antagonist prazosin. In addition, SKF83959 inhibited the afferent volley and significantly reduced the pairedpulse facilitation ratios. In dissociated hippocampal CA1 pyramidal neurons, SKF83959 had no detectable effect on glutamate-induced currents but potently inhibited voltage-activated Na 1 current (IC50 value 5 26.9 6 1.0 lM), which was not blocked by SCH23390 or by intracellular dialysis of GDP-b-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 1 channel in the afferent fibers. The suppression of excitatory synaptic transmission and the Na 1 channel by SKF83959 may contribute to its therapeutic benefits in Parkinson's disease. V