Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Recently, many life style aspects like diet and environmental factors contribute to the abundance of numerous diseases like Parkinson disease (PD). Cannabinoid (CB) receptors are one of the most abundant G-protein coupled receptors in the brain raising interest regarding their role. Though preclinical studies demonstrated the benefit of modulating the cannabinoid system in PD, results from clinical settings are controversial and inconclusive. Many studies suggest protective effect of activating the endocannabinoid system (ECS), while others show the benefit of antagonizing the ECS action. Therefore, the current study addressed the effect of the synthetic cannabinoid agonist WIN55,212-2 and/or rimonabant a synthetic CB1 receptor antagonist/inverse agonist in a PD model induced by reserpine in rats. Adult male Sprague-Dawley rats were divided into 5 groups; group 1 was the control group that received the vehicle. In the 4 other groups, rats were subcutaneously injected with reserpine (3 mg/kg). Rats in the PD group were left untreated, whereas those in the other 3 group were given WIN55,212 (0.1 mg/kg, i.p; group 3), a cannabinoid agonist, rimonabant (0.1 mg/kg, i.p; group 4), a cannabinoid inverse agonist or a combination of both (group 5) 24 h after reserpine. The post-administration of WIN55,212-2 neither affected substantia nigral (SNPc) histopathological alterations nor the reduced substantia nigral/striatal tyrosine hydroxylase (TH) immunoreactivity and striatal dopamine content induced by reserpine. Conversely, the post-administration of rimonabant reversed the injurious effect of reserpine on the SNPc histopathology, the SNPc/striatal TH immunoreactivity and striatal dopamine content

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