Effects of pharmacologic catecholamine manipulation on smooth pursuit eye movements in normals.
The pathophysiology of schizophrenia may be related directly or indirectly to abnormal dopaminergic activity. Both subcortical excess and frontal cortical deficiency of dopamine have been suggested, and primary or downstream failures of dopamine activation to the prefrontal cortex has been posited to explain some of the cognitive deficiencies in schizophrenia patients. Although the prefrontal cortex may also be a site for the disruption of smooth pursuit eye movements (SPEM), the most substantially described psychophysiological marker for schizophrenia vulnerability, no relationship of SPEM to dopaminergic activity has been demonstrated. In this study we explored the effect of altered dopamine function on SPEM quality through pharmacological manipulation of catecholamine tone in 11 healthy subjects. The subjects had SPEM measured 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 the agents. Placebo 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 characteristic of patients with schizophrenia. These findings link dopaminergic blockade with SPEM disruption in normal subjects.
Malaspina
D
D
Department of Clinical Psychobiology, New York State Psychiatric Institute, NY 10032.
Colemann
E A
EA
Quitkin
M
M
Amador
X F
XF
Kaufmann
C A
CA
Gorman
J M
JM
Sackeim
H A
HA
D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010555:Personality Inventory; D011698:Pursuit, Smooth / Q000187:drug effects* / Q000502:physiology
D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine