The present study explored the involvement of
cyclooxygenase (COX) in the pathophysiology of
Parkinson's disease (PD). Further, the protective effect of COX-inhibitors against
perphenazine-induced
catatonia and 1-methyl-4-phenyl-1, 2, 3, 6-tertahydropyridine (
MPTP)-induced striatal lesions in rats was evaluated. Administration of
perphenazine (5 mg/kg., i.p.) produced severe
catatonia (rigid behavior) in rats; the maximum score reached at 4 h (estimated as 100% AUC) and declined within 24 h. An intrastriatal injection of
MPTP produced hypolocomotor activity in rats. Both
perphenazine and
MPTP produced oxidative stress as demonstrated by increased levels of
lipid peroxides,
nitrite and decreased
antioxidant defense system in the whole brain and striatal region, in particular. Pretreatment with various COX-inhibitors viz.
rofecoxib,
celecoxib,
nimesulide or
naproxen offered protection against
perphenazine-induced
catatonia, the effect was more pronounced with
rofecoxib.
Rofecoxib and
celecoxib (both selective
COX-2 inhibitors) also reversed the
perphenazine-induced oxidative stress. Further, prior treatment with
rofecoxib (8 mg/kg, p.o.) reversed both the behavioral and biochemical changes induced by
MPTP. These results suggest that COX-inhibitors particularly,
rofecoxib offers protection against
drug-induced
catatonia and
MPTP-induced striatal lesions possibly by modulating dopaminergic neurotransmission and/or oxidative stress.