Abstract
The effects of apomorphine (0.01 mg/kg SC) a direct- acting dopamine (DA) agonist, MK-212 (6-chloro-2-[1- piperazinyJ-pyrazine) (20 mg PO), a direct-acting serotonin (5-HT) agonist, and placebo on smooth pursuit fYe 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. Tie 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.
Original language | English (US) |
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Pages (from-to) | 49-62 |
Number of pages | 14 |
Journal | Neuropsychopharmacology |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Aug 1994 |
Funding
This research was supported by USPHS grants MH-47574 (to Dr. Friedman), MH-41684 (to Dr. Meltzer) and GCRC M01RR00080, by the Department of Veterans Affairs and grants to Dr. Meltzer from the Elisabeth Severance Prentiss, John Pascal Sawyer and Laureate Foundations. HYM is the recipient of a USPHS Research Career Scientist Award (MH 47808).
Keywords
- Apomorphine
- Dopamine
- Gain
- MK-212
- Normal volunteers
- Serotonin
- Smooth pursuit
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology