The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats

• Published in: European journal of pharmacology 2007-04, Vol.560 (2), p.163-175
• Main Authors: Reksidler, Angela B., Lima, Marcelo M.S., Zanata, Sílvio M., Machado, Hidevaldo B., da Cunha, Cláudio, Andreatini, Roberto, Tufik, Sergio, Vital, Maria A.B.F.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; COX-2; Cyclooxygenase 2 Inhibitors - pharmacology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Exploratory Behavior - drug effects; Hippocampus - drug effects; Isoxazoles - pharmacology; Male; Maze Learning; Medical sciences; Motor Activity - drug effects; MPTP; MPTP Poisoning - drug therapy; MPTP Poisoning - enzymology; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neuroprotective Agents - pharmacology; Parecoxib; Parkinson's disease; Pharmacology. Drug treatments; Rats; Rats, Wistar; Tyrosine 3-Monooxygenase - analysis; Tyrosine hydroxylase
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.12.032

The present study investigated the effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib (Bextra™) in the prevention of motor and cognitive impairments observed in rats after an intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a model of the early phase of Parkinson's disease. The treatment with parecoxib (10 mg/kg) administered prior to the surgery and daily (2 mg/kg) for the subsequent 21 days, prevented the MPTP-treated rats from presenting decreased locomotor and exploratory behavior, increased immobility, and impairment while performing the cued version of the Morris water maze. Furthermore, parecoxib treatment also significantly prevented the reduction of tyrosine hydroxylase protein expression in the substantia nigra (7, 14 and 21 days after surgery), and in the striatum (14 and 21 days after surgery) as immunodetected by western blotting. These results strongly suggest that parecoxib exerts a neuroprotective effect on motor, tyrosine hydroxylase expression, and cognitive functions as it prevents their impairments within the confines of this animal model of the early phase of Parkinson's disease.