5-HT[1A] receptor activation improves anti-cataleptic effects of levodopa in 6-hydroxydopamine-lesioned rats

ABSTRACT

In Parkinson_s disease [PD] prolong use of L-DOPA causes some motor disorders such as wearing-off and L-DOPA induced dyskinesia [LID]. In this investigation the effect of 8-OHDAPT, as a 5-HT[1A] agonist on anti-cataleptic effect of L-DOPA in 6-hydroxydopamine [6-OHDA] lesioned male Wistar rats was investigated. Catalepsy was induced by unilateral injection of 6-OHDA [8 micro g/2 micro l/rat] into the central region of the SNc. After 3 weeks as a recovery period, animals received intraperitoneally [i.p.] L-DOPA [15 mg/kg] twice daily for 20 days, and anti-cataleptic effect of L-DOPA was assessed by bar-test at days of 5, 10, 15 and 20. The results showed that L-DOPA had anti-cataleptic effect only until the day of 15, and its effect was decreased on the day of 20. On the day of 21, rats were co-injected with three different doses of 8-OHDAPT [0.1, 0.5 and 2.5 mg/kg, i.p.] and L-DOPA [15 mg/kg, ip]. 8-Hydroxy-2-[di-n-propylamino] tetralin [8-OHDAPT] improved anti-cataleptic effect of L-DOPA at the dose of 0.5 mg/kg. Moreover the effect of 8-OHDAPT on anti-cataleptic effect of L-DOPA [15 mg/kg, ip] was abolished by 1-[2-methyoxyphenyl]-4-[4-[2-phthalamido] butyl] piperazine hydrobromide [NAN-190; 0.5 mg/kg, i.p.] as a 5-HT[1A] receptor antagonist. According to the obtained results, it may be concluded that activation of 5-HT[1A] receptors by 8-OHDAPT may improve anti-cataleptic effect of L-DOPA in a 6-OHDA- induced rat model of PD. Further studies are required to clarify the exact mechanism of interaction between 5-HT[1A] and dopaminergic neurons