8-OH-DPAT (5-HT1A agonist) Attenuates 6-Hydroxy-dopamine-induced catalepsy and Modulates Inflammatory Cytokines in Rats

Abstract

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 8-OH-DPAT on 6-OHDA-induced catalepsy and levels of inflammatory cytokines in cerebrospinal fluid (CSF). Materials and Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 mu g/2 mu l/rat) into the central region of the sabstantia nigra pars compacta (SNc) being assessed by the bar-test, 5, 60, 120 and 180 min after intraperitoneal (IP) administration of 8-OH-DPAT (5-HT1A receptor agonist; 0.25, 0.5 and 1mg/kg, IP for 10 days). CSF samples were collected on the tenth day of 8-OH-DPAT administration and analyzed by ELISA method to measure levels of TNF-alpha, IL-1 beta and IL-6. Results: Chronic injection of 8-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 1 mg/kg of 8-OH-DPAT. Levels of TNF-alpha in CSF increased three weeks after 6-OHDA injection while there was a significant decrease in TNF-alpha level of parkinsonian animals treated with 8-OH-DPAT (1 mg/kg, IP for 10 days). IL-1 beta and IL-6 decreased and increased in parkinsonian rats and in 8-OH-DPAT-treated parkinsonian rats, respectively. Conclusion: Our study indicated that chronic administration of 8-OH-DPAT improves catalepsy in 6-OHDA-induced animal model of PD and restores central concentration of inflammatory cytokines to the basal levels. 5-HT1A receptor agonists can be suggested as potential adjuvant therapy in PD by modulation of cerebral inflammatory cytokines.