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

Abstract

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). Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/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-α, IL-1β and IL-6. 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-α in CSF increased three weeks after 6-OHDA injection while there was a significant decrease in TNF-α level of parkinsonian animals treated with 8-OH-DPAT (1 mg/kg, IP for 10 days). IL-1β and IL-6 decreased and increased in parkinsonian rats and in 8-OH-DPAT-treated parkinsonian rats, respectively. 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.