Chronic SKF83959 induced less severe dyskinesia and attenuated L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease

Endogenous Dopamine Regulates the Rhythm of Expression of the Clock Protein PER2 in the Rat Dorsal Striatum via Daily Activation of D2Dopamine Receptors

“…To investigate whether such treatments could also restore the normal rhythm of PER2 expression in the 6-OHDA-lesioned dorsal striatum, we gave systemic injections of the D 1 DA agonist, SKF 81297 (1 mg/kg), the D 2/3 DA agonist, quinpirole (0.5 mg/kg), or vehicle (1 ml/kg) at ZT1 for 10 d, beginning 15 d after surgery. Drug doses were in the range shown previously to enhance expression of immediate-early genes, striatal peptides, and electrophysiological responses of striatal neurons in 6OHDA-lesioned rats (Gerfen et al, 1990(Gerfen et al, , 1995Hu et al, 1992;Zhang et al, 2007;Ballion et al, 2009). We chose to give the daily agonist injection at ZT1, a time at which extracellular DA levels in the striatum are normally low, to determine whether exogenous stimulation of DA receptors would not only restore PER2 expression in the lesioned striatum, but also establish a new rhythm of PER2 expression whose phase was determined by the time of the agonist injection.…”

Activation of Phosphatidylinositol-Linked D1-Like Receptor Modulates FGF-2 Expression in Astrocytes via IP3-Dependent Ca2+ Signaling

“…SKF83959 [3-methyl-6-chloro-7,8-hydroxy-1-(3-methylphenyl)-2,3,4,5-tet-rahydro-1 H-3-benzazepine], a recently identified PI-linked D 1 -like receptor agonist, selectively stimulates PI hydrolysis via Gq-mediated activation of phospholipase C ␤ (PLC␤) (Frail et al, 1993;Jin et al, 2003). The powerful antiparkinsonian action of SKF83959 is believed to associate with the drug-elicited PLC␤/ PI-hydrolysis (Zhen et al, 2005;Zhang et al, 2007). Moreover, chronic SKF83959 treatment was found to attenuate the development of levodopa-induced dyskinesia (Andringa et al, 1999;Zhen et al, 2005;Zhang et al, 2007).…”

Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study

“…SKF83959 has been shown to produce potent anti-parkinsonian effects in primate and rodent models [5][6][7] , and chronic administration of SKF83959 also attenuates the development of L-DOPA-induced dyskinesia (LID) in 6-OH-DOPA-lesioned rat models; this latter result may be associated with the drug's neuroprotective effects [5,8] . We have previously reported that SKF83959 has potent neuroprotective effects that are only partially attributable to D1-like receptor activation [10] .…”

“…It has been shown that SKF83959 produces potent antiparkinsonian effects in primate and rodent models [5][6][7] . Furthermore, SKF83959 has been reported to attenuate L-DOPAinduced dyskinesia (LID) in 6-OH-DOPA-lesioned rat models [5,8] . Recently, SKF83959 has been shown to be an identified allosteric modulator of the sigma-1 receptor and to have antidepressant effects [9] ; moreover, SKF83959 has also been shown to improve the survival of pheochromocytoma cells (PC12 cells) subjected to H 2 O 2 insult [10] .…”

“…Recently, SKF83959 has been shown to be an identified allosteric modulator of the sigma-1 receptor and to have antidepressant effects [9] ; moreover, SKF83959 has also been shown to improve the survival of pheochromocytoma cells (PC12 cells) subjected to H 2 O 2 insult [10] . Both D1 receptor-dependent and -independent mechanisms have been suggested to be responsible for the range of the drug's effects [5][6][7][8]10] .…”