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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.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.