FK506 as effective adjunct to L-dopa in reserpine-induced catalepsy in rats.

ABSTRACT

Reserpine-induced catalepsy is a widely accepted animal model of Parkinson's disease. In the present study reserpine (2.5 mg/kg, ip) 20 hr and alpha-mehyl-para-tyrosine (AMPT; 200 mg/kg, ip), one hour before the experiment induced significant catalepsy in rats as assessed by bar test. There was a significant increase in the time spent on the bar in bar test as compared to the control untreated rats. L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination, a conventional therapy was less effective in reversing reserpine-induced catalepsy. Pretreatment with FK506, a neuroprotectant (0.5-2 mg/kg, po) not only dose dependently reduced the catalepsy in reserpine-treated rats but a lower dose (1 mg/kg) potentiated the motor stimulant actions of sub threshold dose of L-dopa (100 mg/kg, ip) and carbidopa (10 mg/kg, ip) combination. Anticataleptic effect of FK506 was blocked dose dependently by specific D2 receptor blocker sulpiride (25-100 mg/kg, ip). In conclusion, the findings of the present study suggest that FK506 has an indirect modulatory action on the dopamine D2 receptors. FK506 being a neuroprotectant, could be used as an effective adjunct to L-dopa for the treatment of neuroleptic-induced extrapyramidal side effects.