Increasing doses of l-sulpiride reveal dose- 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 electroretinographic responses to three different spatial frequency grating stimuli (0.25, 1 and 4 c/deg), reversed at 7.5 Hz, were studied in normal 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 effect of the drug on the pattern electroretinogram (PERG) was clearly dose-dependent, being greatest on the responses to 4 c/deg. The mean decrease in second harmonic amplitude was -13.8% after 0.071 mg/kg of l-sulpiride, -23.5% after 0.357 mg/kg and -28.5% after 1.428 mg/kg. The last two variations were significant at P <0.01 and P <0.01 respectively. These data suggest that a dose-dependent effect on the human retinal response to 4 c/deg stimuli exists, probably mediated by a coupling between l-sulpiride and D2 receptors. Lastly, our data suggest that D2 receptors may play an important role in the pathophysiology of visual dysfunction in Parkinson's disease, that has been described to be more significant at medium spatial frequency (2-5 c/deg).