Effects of dopaminergic agents on eye tracking before and after repeated methamphetamine

The effects of methamphetamine (MA), apomorphine (AP) and haloperidol (HAL) on eye tracking function were tested in rhesus monkeys. Three rhesus monkeys were trained to track with their eyes a disk-shaped projected image that oscillated along a horizontal plane on a screen, using a training procedure in which responses on a lever were reinforced with water only when the center of the disk dimmed for a brief period. Eye movements were recorded by electrooculography (EOG). The effects of intramusuclar administration of MA, APO and HAL on responding were compared before and after a 8-14 day period of repeated MA administration. During this regimen, MA was given in 4 divided doses starting at a total daily dose of 4 mg/kg/day and increasing to 16-40 mg/kg/day. All three drugs disrupted performance during both the initial dose-response determination as well as during the redetermination following the regimen. However, tolerance to MA in 3 monkeys and to APO in 2 monkeys was observed after the regimen, while no marked sensitivity change was observed to haloperidol. Since other data reported elsewhere have shown that dopamine is depleted in the caudate after similar repeated administration regimens, long lasting brain dopaminergic changes are likely present in these monkeys. Therefore, these results suggest that the changes in sensitivity to the drugs that were observed in terms of eye tracking function are related to dopamine depletion in the brain.