title: Vinpocetine attenuates MPTP-induced motor deficit and biochemical abnormalities in Wistar rats.
abstract: Up-regulation in phosphodiesterase 1 (PDE1) expression and decreased levels of cyclic nucleotides (cAMP and cGMP) have been reported in patients and experimental animal models of Parkinson's disease (PD). Phosphodiesterase (PDE) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study is designed to investigate the effect of vinpocetine, a PDE1 inhibitor in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental PD-like symptoms in rats. To produce stable motor deficit, MPTP was repeatedly administered intranigrally (bilaterally) at an interval of 1 week (days 1, 7 and 14). Following development of stable motor deficit, which was observed after the third infusion of MPTP (day 14) in rats, the animals were treated with vinpocetine (5-, 10- and 20-mg/kg, i.p.) from days 15 to 28. Movement abnormalities were assessed by a battery of behavioral tests. Moreover, levels of malondialdehyde, nitrite and reduced glutathione were measured in striatal brain homogenate to confirm the role of oxidative and nitrosative stress in PD. Repeated intranigral administration of MPTP produced stable motor deficits, reduced the cyclic nucleotides and dopamine levels and caused elevation in oxidative-nitrosative stress markers. Chronic administration of vinpocetine (for 14 days) significantly and dose dependently attenuated movement disabilities and oxidative-nitrosative stress in MPTP-treated rats. Moreover, vinpocetine treatment enhances cyclic nucleotide levels and restores the dopamine level in MPTP-treated rats. The observed results of the present study are indicative of the therapeutic potential of vinpocetine in PD.
authors.affiliation: Neuropharmacology Division, ISF College of Pharmacy, Moga 142001, Punjab, India.
authors.forename: S
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Neuropharmacology Division, ISF College of Pharmacy, Moga 142001, Punjab, India. Electronic address: login2rd@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Deshmukh
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004660:Encephalitis / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D020734:Parkinsonian Disorders / Q000188:drug therapy*; D065842:Pars Compacta / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D014748:Vinca Alkaloids / Q000008:administration & dosage*
chemical_list: D010726:Phosphodiesterase Inhibitors; D014748:Vinca Alkaloids; C013983:vinpocetine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000242:Cyclic AMP; D006152:Cyclic GMP
keywords: MPTP; PDE1; Parkinson’s disease; cyclic nucleotides; phosphodiesterases; vinpocetine