۸-OH-DPAT (۵-HT۱A agonist) Attenuates ۶-Hydroxy- dopamine-induced catalepsy and Modulates Inflammatory Cytokines in Rats

  Objective(s): Neuroinflammation in Parkinson disease (PD) is associated with glial cells activation and production of different inflammatory cytokines. In this study, we investigated the effect of chronic administration of ۸-OH-DPAT on ۶-OHDA-induced catalepsy and levels of inflammatory cytokines in cerebrospinal fluid (CSF).   Materials and Methods: Catalepsy was induced by unilateral infusion of ۶-OHDA (۸ μg/۲ μl/rat) into the central region of the sabstantia nigra pars compacta (SNc) being assessed by the bar-test, ۵, ۶۰, ۱۲۰ and ۱۸۰ min after intraperitoneal (IP) administration of ۸-OH-DPAT (۵-HT۱A receptor agonist; ۰.۲۵, ۰.۵ and ۱mg/kg, IP for ۱۰ days). CSF samples were collected on the tenth day of ۸-OH-DPAT administration and analyzed by ELISA method to measure levels of TNF-α, IL-۱β and IL-۶. Results: Chronic injection of ۸-OH-DPAT decreased catalepsy in a dose dependent manner when compared with the control group. The most anti-cataleptic effect was observed at the dose of ۱ mg/kg of ۸-OH-DPAT. Levels of TNF-α in CSF increased three weeks after ۶-OHDA injection while there was a significant decrease in TNF-α level of parkinsonian animals treated with ۸-OH-DPAT (۱ mg/kg, IP for ۱۰ days). IL-۱β and IL-۶ decreased and increased in parkinsonian rats and in ۸-OH-DPAT-treated parkinsonian rats, respectively. Conclusion: Our study indicated that chronic administration of ۸-OH-DPAT improves catalepsy in ۶-OHDA-induced animal model of PD and restores central concentration of inflammatory cytokines to the basal levels. ۵-HT۱A receptor agonists can be suggested as potential adjuvant therapy in PD by modulation of cerebral inflammatory cytokines.