Cognitive and motor deficits in the acquisition of an object retrieval/detour task in MPTP-treated monkeys.
To assess functional changes following treatment with 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) in monkeys, we studied a task that reveals sensitivity to dopamine deficits under various conditions. The task required retrieval of a banana slice from a transparent box that is open on one side and fastened to a tray. Successful performance required the subject to suppress a tendency to reach directly at the reward while (1) orientation of the open side, (2) position on the tray, and (3) position of the banana in the box were manipulated in order to vary the cognitive and motor difficulty of the trial. African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative dose over 4-5 days). A control group was sham treated (n = 12). MPTP-treated subjects either became severely symptomatic, showing motor impairments that prevented them from performing, or showed no gross motor impairment (n = 6) in spite of major depletions in dopamine concentrations. MPTP-treated subjects showed impaired acquisition of the task when tested 8-12 months later. They made more errors during the sessions, specifically on the trials that were related to cognitive complexity, such as attempting to reach directly towards the reward through the transparent side of the box (a barrier reach), instead of reaching around it (detour) into the open side, as well as other awkward, perseverative or delayed reaches. MPTP appears to cause both cognitive and motor deficits in the acquisition of this task 8-12 months after treatment, even in the group of monkeys which never showed gross motor deficits.
Taylor
J R
JR
Neurobehavioral Laboratory, Yale University School of Medicine, New Haven, CT 06510-8068.
Elsworth
J D
JD
Roth
R H
RH
Sladek
J R
JR
Redmond
D E
DE
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002522:Chlorocebus aethiops; D003071:Cognition / Q000187:drug effects*; D006719:Homovanillic Acid / Q000378:metabolism; D007858:Learning / Q000187:drug effects*; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006719:Homovanillic Acid