title: Buspirone improves the anti-cataleptic effect of levodopa in 6-hydroxydopamine-lesioned rats.
abstract: In Parkinson's disease (PD), prolonged exposure to L-3,4-dihydroxyphenylalanine (L-DOPA) results in motor fluctuations, such as the on-off phenomenon, and L-DOPA-induced dyskinesia. Previously, we found that activation of 5-HT(1A) in the substantia nigra pars compacta (SNc) decreased catalepsy in parkinsonian rats. In the current investigation, we attempted to evaluate the effect of buspirone on the anti-cataleptic effect of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned male Wistar rats. Catalepsy was induced by the unilateral infusion of 6-OHDA (8 μg/2 μl/rat) into the central region of the SNc. After a 3-week recovery period, rats received L-DOPA intraperitoneally (ip; 15 mg/kg) twice daily for 20 days, and the anti-cataleptic effect of L-DOPA was assessed by the bar test at days 5, 10, 15 and 20. The results showed that L-DOPA had an anti-cataleptic effect only until day 15, and its effect was abolished on day 20. On day 21, these rats were co-treated with three different doses of buspirone (0.1, 0.5 and 2.5 mg/kg, ip) and L-DOPA (15 mg/kg, ip). At a dose of 0.5 mg/kg, buspirone improved the anti-cataleptic effect of L-DOPA. Furthermore, the effect of buspirone (0.5 mg/kg, ip) on the anti-cataleptic effect of L-DOPA (15 mg/kg, ip) was reversed by 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)piperazine hydrobromide (NAN-190; 0.5 mg/kg, ip), a 5-HT(1A) receptor antagonist. From these results, it may be concluded that buspirone improves the anti-cataleptic effect of L-DOPA in a 6-OHDA-induced animal model of PD through the activation of 5-HT(1A) receptors. In this regard, further investigations should be undertaken to clarify the exact mechanism of the interaction between 5-HT(1A) and dopaminergic neurons.
authors: Department of Pharmacology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
authors: Javad
authors: J
authors: Mahmoudi
authors: Alireza Mohajjel
authors: AM
authors: Nayebi
authors: Morteza
authors: M
authors: Samini
authors: Siamak
authors: S
authors: Reyhani-Rad
authors: Vahab
authors: V
authors: Babapour
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D007980:Levodopa; D016627:Oxidopamine; D002065:Buspirone