Abstract
The effects of apomorphine (0.01 mg/kg SC) a direct-acting dopamine (DA) agonist, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) (20 mg PO), a direct-acting serotonin (5-HT) agonist, and placebo on smooth pursuit eye movements were evaluated in 10 to 12 normal volunteers. Smooth pursuit was tested just prior to administration of either apomorphine, MK-212, or placebo (on separate days), and then repeatedly tested at 30 min intervals for two hours after dose administration. The smooth pursuit targets were a series of predictable, constant velocity ramps with velocities of 5°/sec (slow target) and 20°/sec (fast target). Eye movements were recorded with infrared oculography, and the following six measures were obtained; steady-state gain (slow-target-gain; fast-target-gain), corrective catch-up saccade (CUS) rate (slow-target-CUS-rate; fast-target-CUS-rate), and CUS amplitude (slow-target-CUS-amplitude; fast-target-CUS-amplitude). The placebo test yielded a statistically significant monotonic decrease over time in slow-target-gain and corresponding increase in slow-target-CUS-rate, but no effects of placebo were noted for the fast target. Apomorphine injection produced a marked reduction in both slow-target-gain and fast-target-gain at 30 min, returning to baseline thereafter. Apomorphine injection also produced a statistically significant increase in slow-target-CUS-amplitude. Ingestion of MK-212 produced a statistically significant increase in slow-target-gain and fast-target-gain as well as a corresponding decrease in slow-target-CUS-rate and fast-target-CUS-rate at 90 min or 120 min. There was evidence that the decline in slow-target-gain after apomorphine was associated with side-effects such as sleepiness, but the decline in fast-target-gain was not related to side-effects. The improved smooth pursuit performance after MK-212 was not related to side-effects. The data suggest that serotoninergic stimulation can improve smooth pursuit performance, whereas dopaminergic stimulation worsens this performance.
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Address reprint requests to Lee Friedman, Ph.D., Department of Pyschiatry, Hanna Pavilion, Room B 68, Case Western Reserve University, Cleveland, OH 44106.
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Friedman, L., Jesberger, J. & Meltzer, H. The Effect of Apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and Placebo on Smooth Pursuit Gain and Corrective Saccades in Normal Subjects. Neuropsychopharmacol 11, 49–62 (1994). https://doi.org/10.1038/npp.1994.35
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DOI: https://doi.org/10.1038/npp.1994.35
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