title: SKF83959 suppresses excitatory synaptic transmission in rat hippocampus via a dopamine receptor-independent mechanism.
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.
authors.affiliation: State Key Laboratory of Drug Research and Department of Pharmacology II, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chu
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Wu
authors.forename: Shanglin
authors.initials: S
authors.lastname: Zhou
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Cao
authors.forename: Ao
authors.initials: A
authors.lastname: Zhang
authors.forename: Guo-Zhang
authors.initials: GZ
authors.lastname: Jin
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Hu
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D001552:Benzazepines; D011954:Receptors, Dopamine; C534628:SCH 23390; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959