Deficits in reaction times and movement times as correlates of hypokinesia in monkeys with MPTP-induced striatal dopamine depletion.
1. We quantitatively assessed deficits in the initiation and execution of arm movements occurring after destruction of nigrostriatal dopamine neurons by systemic administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Sigma). Three monkeys performed a reaction time task in which they reached toward a single and constant target for food reward. 2. After administration of MPTP, all three monkeys showed hypokinesia necessitating dopamine precursor or receptor agonist treatment. The partial recovery of one animal from initial akinesia after 19 days permitted discontinuation of dopaminergic drug therapy, although marked hypokinesia remained present. The two other animals displayed additional, intermittent phases of rigidity and activation tremor and needed continuous dopaminergic drug therapy for most of the postlesion period. 3. Administration of MPTP significantly prolonged EMG reaction time in prime mover muscles and arm movement reaction time by 47-225% and 18-129%, respectively, on the six sides of the three animals, compared with control measurements before the lesion. EMG and arm movement reaction time increased over consecutive trials in most sessions comprising 110-130 movements, the first 20 movements showing almost normal values. The delay time between onsets of EMG and arm movement showed unsystematic changes. These deficits in movement initiation were observed both with and without dopamine precursor therapy. They lasted during the whole testing period of several months. 4. Linear correlations between arm movement onset and EMG onset in the two prime mover muscles, the extensor digitorum communis and the biceps, showed coefficients of mostly 0.7-0.9, both before and after MPTP. These data suggest that the temporal relationship between onsets of arm movement and EMG were not substantially affected by MPTP. 5. Arm movement time was divided into two phases. The duration of movement between the resting key and the target, a small food-containing box located ahead of the animal, was denoted as reaching movement time. The following hand manipulation inside the food box was measured as box movement time. After MPTP, both measures were significantly prolonged by 10-103% and 12-251%, respectively, on the six sides of the three monkeys. These deficits in movement execution were observed both with and without dopaminergic drug therapy and during the whole testing period. 6. Task performance after MPTP treatment was studied in one monkey in the absence of dopaminergic drug therapy. EMG and arm movement reaction times recovered partially over several weeks, while the prolongations in reaching and box movement times remained unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)
Schultz
W
W
Institut de Physiologie, Université de Fribourg, Switzerland.
Studer
A
A
Romo
R
R
Sundström
E
E
Jonsson
G
G
Scarnati
E
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001132:Arm / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008251:Macaca / Q000502:physiology*; D008252:Macaca fascicularis / Q000502:physiology*; D008297:Male; D009068:Movement; D009069:Movement Disorders / Q000139:chemically induced / Q000503:physiopathology*; D009132:Muscles / Q000503:physiopathology; D011725:Pyridines / Q000633:toxicity*; D011930:Reaction Time / Q000502:physiology*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine