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

Document Type: Original Article

Authors

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

3 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

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 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.
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-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.
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.

Keywords


 

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