INCREASING DOSES OF L-SULPIRIDE REVEAL DOSE-DEPENDENT AND SPATIAL FREQUENCY-DEPENDENT EFFECTS OF D2 SELECTIVE BLOCKADE IN THE HUMAN ELECTRORETINOGRAM

The amplitude and phase of the second harmonic (15 Hz) of the electror etinographic responses to three different spatial frequency grating st imuli (0.25, 1 and 4 c/deg), reversed at 7.5 Hz, were studied in norma l human subjects, before and 30 min after the systemic administration of three doses (0.071, 0.357 or 1.428 mg/kg) of a selective D2 blocker , l-sulpiride, to three populations of 18, 19 or 20 subjects, The effe ct of the drug on the pattern electroretinogram (PERG) was clearly dos e-dependent, being greatest on the responses to 4 c/deg. The mean decr ease in second harmonic amplitude was -13.8% after 0.071 mg/kg of l-su lpiride, -23.5% after 0.357 mg/kg and -28.5% after 1.428 mg/kg. The la st two variations were significant at P < 0.01 and P < 0.01 respective ly. These data suggest that a dose-dependent effect on the human retin al response to 4 c/deg stimuli exists, probably mediated by a coupling between l-sulpiride and D2 receptors. Lastly, our data suggest that D 2 receptors may play an important role in the pathophysiology of visua l dysfunction in Parkinson's disease, that has been described to be mo re significant at medium spatial frequency (2-5 c/deg).