Neuroprotective Effects of GSK-3β Inhibition and D1 Agonism on L-dopa-induced Dyskinesia

Apomorphine hydrochloride (Sigma-Aldrich, St. Louis, MO, USA) was administered (0.5 mg/kg). L-dopa (Sigma-Aldrich, 25 mg/kg) plus benserazide-HCl (Sigma-Aldrich, 6.25 mg/kg) were given once-daily. TDZD8, a non-ATP competitive inhibitor of GSK-3β, was dissolved in 10% DMSO and was administered i.p. (TDZD8-L group, 1 mg/kg; TDZD8-H group, 2 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks. The dose of TDZD8 used was based on previous studies23 (link). (±)-1-Phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF38393, Abcam, UK), a D1 Dopamine receptor agonist, was dissolved in saline and was administered i.p. (SKF38393-L group, 5 mg/kg; SKF38393-H group, 10 mg/kg, respectively) 30 min prior to L-dopa intake for 3 weeks. The dose of TDZD8 used was based by Iderberg et al.24 (link). The dose of L -dopa (25 mg/kg) was chosen by our previous study25 (link).