Abstract
Purpose: The exact pathogenesis of sporadic
parkinson’s disease (PD) is still unclear. Numerous evidences suggest
involvement of apoptosis in the death of dopaminergic neurons. In this study we
investigated the effect of sub-chronic administration of buspirone, fluoxetine
and 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine
(6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax,
Caspase3) and anti-apoptotic (Bcl-2) proteins.
Methods: 6-OHDA (8μg/2μl/rat) was injected
unilaterally into the central region of the substantia nigra pars copmacta
(SNc) of male Wistar rats and then, after 21 days lesioned rats were treated
with intraperitonel (i.p) 1 mg/kg injections of buspirone, fluoxetine and
8-OH-DPAT for 10 consecutive days. Striatum of rats was removed at tenth day of
drugs administration and were analyzed by western blotting method to measure
Bax, caspase3 and Bcl-2 expression.
Results: The results showed that the expression of Bax and caspase3 proteins was
increased three weeks after 6-OHDA injection while they were decreased
significantly in parkinsonian rats which were treated by buspirone, fluoxetine
and 8-OH-DPAT. Bcl-2 was decreased and increased in parkinsonian rats and
parkinsonian rats treated with buspirone, fluoxetine and 8-OH-DPAT,
respectively.
Conclusion: Our study indicates that sub-chronic
administration of serotonergic drugs such as buspirone, fluoxetine and
8-OH-DPAT restores striatal concentration of apoptotic and anti-apoptotic
factors to the basal levels of normal non-lesioned rats. We suggest that these
drugs can be used as a potential adjunctive therapy in PD through attenuating
neuronal apoptotic process.