Dipyridamole potentiates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinsonism in mice.
Adenosine is an endogenous neuromodulator which alters neuronal excitability and firing rate. In recent years there has been growing interest in the manipulation of adenosine levels to understand the pathophysiology of various diseases. Dipyridamole (DPM) is a potent adenosine transport inhibitor that causes a several-fold increase in brain adenosine concentration. The present study was undertaken to investigate the effect of DPM on MPTP-induced neurotoxicity. Mice weighing 30 +/- 3 g were administered with MPTP (30 mg/kg, i.p.) daily for 5 days. DPM was given daily 1 h before MPTP in doses of 250, 500 and 1000 mg/kg body weight, (P.O.) respectively, in three different groups of mice for 7 days. Twenty four hours after the last dose of DPM, the animals were observed for neurobehavioral changes including locomotor activity and pole descending time. Immediately after behavioral studies, all the animals were sacrificed and brains were isolated for biochemical studies. The treatment of mice with MPTP or DPM individually produced no significant change in mobility or spasticity; however, the combination of these drugs produced significant bradykinesia. There was no incidence of mortality when the mice were treated with MPTP or DPM individually, though the combination of MPTP and DPM produced significant mortality which was proportional to the doses of the later drug. The treatment of mice with MPTP produced significant depletion of striatal dopamine and glutathione. Concomitant treatment of DPM with MPTP further reduced the striatal glutathione level without affecting dopamine. The result of this study shows the ability of DPM to potentiate MPTP-induced neurobehavioral toxicity and mortality in mice. Further studies are warranted to determine the role of adenosine in experimental and clinical Parkinson's disease.
Tariq
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Neuroscience Research Group, Armed Forces Hospital, P.O. Box 7897, Riyadh 11159, Saudi Arabia.
Khan
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HA
Moutaery
K A
KA
Deeb
S A
SA