Effect of Chronic Administration of Buspirone and Fluoxetine on Inflammatory Cytokines in 6-Hydroxydopamine-lesioned Rats.
Neuro-inflammation in Parkinson's disease (PD) is associated with glial cell activation and production of different inflammatory cytokines. In this study we investigated the effect of chronic administration of buspirone and fluoxetine on cerebrospinal fluid (CSF) levels of inflammatory cytokines, TNF-α, IL-1β and IL-6 in 6-hydroxydopamine (6-OHDA)-lesioned rats.6-OHDA (8 μg/2 μl/rat) was injected unilaterally into the central region of the substantia nigra pars copmacta (SNc) and after 21 days lesioned rats were treated with buspirone and fluoxetine intraperitonealy (i.p.) for 10 days. CSF samples were collected at tenth day of drugs administration and were analysed by ELISA method to measure TNF-α, IL-1β and IL-6 levels.The results showed that the CSF levels of TNF-α was increased 3 weeks after 6-OHDA injection while there was a significant decrease in TNF-α levels of parkinsonian animals treated with buspirone (1 mg/kg) and fluoxetine (1 mg/kg). IL-1β and IL-6 both were decreased in parkinsonian rats, while their level was increased in buspirone (1 mg/kg) and fluoxetine (1 mg/kg) treated parkinsonian rats.Our study indicates that chronic administration of buspirone and fluoxetine in 6-OHDA-lesioned rats restores central concentration of inflammatory cytokines to the basal levels. We suggest that serotonergic agents can be used as adjuvant therapy along with commonly used anti-parkinsonian drugs by modulation of cerebral inflammatory cytokines. We suggest that the further clinical investigations may be carried out to prove this hypothesis.
Department of Pharmacology, Faculty of Pharmacy, Urmia University of Medical Science,Urmia, Iran.
H
H
Sharifi
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
A M
AM
Nayebi
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
S
S
Farajnia
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
R
R
Haddadi
D000818:Animals; D002065:Buspirone / Q000008:administration & dosage*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage*; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D016627:Oxidopamine / Q000008:administration & dosage*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D016627:Oxidopamine; D002065:Buspirone