Neuroinflammation plays a key role in progressive degeneration of dopaminergic cells. Upregulation of
prostaglandins and
free radicals formation are involved in the mechanisms of cell death in
Parkinson's disease (PD). The present study aimed to investigate the
neuroprotective effect of
diclofenac against
chlorpromazine (CPZ) induced
catalepsy and motor impairment in mice. Adult Wistar rats treated with CPZ (3 mg/kg/day, IP) were orally dosed with
diclofenac and
L-dopa/
carbidopa for 21 days.
Catalepsy was measured after 21 days of dosing by using standard bar test at 30, 60, 90, 120 and 180 min then motor performances were assessed via open field test and wire hanging test. Histopathological investigation and determination of
dopamine (DA) and
3,4-Dihydroxyphenylacetic acid (
DOPAC) levels of rat's brain was also carried out. We found that CPZ treated group exhibited reduced motor impairment after 21 days of treatment in open field and wire hanging test (P < 0.01) as compared to control group. The cataleptic scores of CPZ treated rats were also significantly increased (P < 0.01) after 21 days of chronic dosing, however
diclofenac treated groups showed significant reduction in cataleptic scores with improved motor performances. Histopathology of CPZ treated rats showed marked degeneration with architecture distortion in the mid brain region. Dopaminergic degeneration is confirmed by neurochemical results that showed reduced amount of
dopamine and
DOPAC levels in mid brain. Moreover, histopathological slides of
diclofenac treated rats showed improved architecture with reduced
gliosis of mid brain region as well as improved
dopamine and
DOPAC levels were achieved after 21 days dosing of
diclofenac. Taken together, the present work provide an evidence that
diclofenac ameliorated behavioral performances by mediating neuroprotection against CPZ induced PD via preventing dopaminergic neuronal cell death.