Low doses of apomorphine transiently reduce locomotor activity in MPTP-treated mice

Parkinson's disease patients sometimes experience deterioration of motor function to below their baseline “off” state, termed the “super-off” state. We used low subthreshold (0.05 mg/kg) to threshold (0.10 and 0.20 mg/kg) doses of apomorphine to demonstrate the “super-off” state in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned mice. Twenty-four mice were randomized to receive apomorphine or vehicle. Within 20 min of administration, 0.10 and 0.20 mg/kg apomorphine-treated mice had less locomotion than controls. At the 100 min time point, 0.10 mg/kg apomorphine-treated mice had greater locomotion than controls. One week of suprathreshold levodopa pretreatment did not alter the response to these low apomorphine doses. Our results suggest that low doses of apomorphine can initially depress locomotion and subsequently stimulate locomotion, in a manner similar to what is seen in Parkinson's disease patients.