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

Abstract

Background and the purpose of the study: In Parkinsons 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. Methods: Catalepsy was induced by unilateral injection of 6-OHDA (8 ?g/2?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. Results and major conclusion: 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.