Effect of fluoxetine on motor disorders induced by intranigral injection of 6-hydroxydopamine in rats

Abstract

Objectives: Parkinson is a neurodegenerative disease characterized by damage of striatal dopaminergic neurons. Recently it has been reported that other neurotransmitter systems, such as serotonergic neurons are involved in pathogenesis of Parkinson disease. Thus, we investigated the effect of fluoxetine, as a specific serotonin reuptake inhibitor, on motor disorders induced by unilateral infusion of 6-OH-dopamine into the substantia nigra, compact part (SNc). Methods: Study was carried out on male Wistar rats weighing between 180-200 g. In oredr to induce experimental model of Parkinson disease, 6-hydoxydopamine (6-OHDA, 8 ?g/rat) was injected unilaterally into the SNc. 6-OHDA-induced catalepsy and balance disturbances were assessed respectively by using bar test and rotarod 5, 60, 120 and 180 minutes after intraperitoneal (i.p.) injections of the drugs. Results: 6-OHDA (8 ?g/rat, Intra-SNc) induced noticeable (P<.01, 0.001) motor disorders of Parkinson disease. Fluoxetine alone (0.1, 0.5 and 1 mg/kg, i.p.) did not produced significant effect (P>0.05) in bar test and rotarod. Whereas, fluoxetine (0.1, 0.5 and 1 mg/kg, i.p.) attenuated (P<0.01, 0.001) and increased (P<.05, 0.01) 6-OHDA induced catalepsy and motor disturbances respectively. In 6-OHDA-lesioned rats, the effect of fluoxetine (0.5 mg/kg, i.p.) on catalepsy and balance disturbances was reversed (P<0.01, 0.001) by NAN-190 (0.5 mg/kg, i.p.). Conclusion: Fluoxetine reduces 6-OHDA-induced catalepsy by affecting on 5-HT1A receptors. Adjuvant therapy with fluoxetine and antiparkinsonian drugs may produce better control in Parkinson disease symptoms.