Effect of chronic subcutaneous minipump infusion of lisuride upon locomotor activity of rats
Male Wistar rats were infused continuously for 14 days with lisuride 0.25mg/kg/day or with vehicle via subcutaneously implanted osmotic mini-pumps. Locomotor activity was measured at 5 hours, 1, 7 and 14 days after implantation. Thereafter the minipumps were removed and 1, 7 and 21 days later the locomotor activity was recorded after a subcutaneous challenge dose of lisuride 0.1 mg/kg. In the course of continuous infusion the lisuride-treated rats showed a persistent stimulation of locomotor activity which remained almost constant throughout the whole period of exposure. At all intervals after removal of the minipumps lisuride challenge produced a less pronounced locomotor stimulation in lisuride-infused rats compared to vehicle-infused animals. This observation contrasts with the findings after chronic subcutaneous bolus treatment of rats with 0.25 mg/kg lisuride once daily for 29 days which resulted (1) in a progressive enhancement of the locomotor stimulatory effect and (2) in a longlasting hyperresponsiveness towards a subcutaneous challenge dose of lisuride 0.025 mg/kg. These results are discussed with respect to the advantage of the constant availability of lisuride at central dopamine receptors for the management of patients with advanced Parkinson’s disease showing fluctuations in motor performance probably related to the kinetics of conventional oral therapy.
KeywordsOsmotic Minipumps Locomotor Stimulation Mini Pump Locomotor Stimulatory Effect Continuous Dopaminergic Stimulation
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