EFFECTS OF PHARMACOLOGICAL CATECHOLAMINE MANIPULATION ON SMOOTH-PURSUIT EYE-MOVEMENTS IN NORMALS

The pathophysiology of schizophrenia may be related directly or indire ctly to abnormal dopaminergic activity. Both subcortical excess and fr ontal cortical deficiency of dopamine have been suggested, and primary or downstream failures of dopamine activation to the prefrontal corte x has been posited to explain some of the cognitive deficiencies in sc hizophrenia patients. Although the prefrontal cortex may also be a sit e for the disruption of smooth pursuit eye movements (SPEM), the most substantially described psychophysiological marker for schizophrenia v ulnerability, no relationship of SPEM to dopaminergic activity has bee n demonstrated. In this study we explored the effect of altered dopami ne function on SPEM quality through pharmacological manipulation of ca techolamine tone in 11 healthy subjects. The subjects had SPEM measure d at baseline, and under challenge conditions including amphetamine (0 .3 mg/kg), haloperidol (2 mg), placebo, and combined amphetamine with haloperidol. Changes in the profile of mood scale (POMS) confirmed the expected subjective central nervous system effects of the agents. pla cebo and amphetamine had no effect on qualitative ratings of SPEM, but haloperidol, alone and in combination with amphetamine, disrupted eye tracking, producing a pattern of small saccadic intrusions characteri stic of patients with schizophrenia. These findings link dopaminergic blockade with SPEM disruption in normal subjects.