Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects

Psychophysical experiments in humans have revealed similar characteristics of visual receptive fields as were found in cats and monkeys from retinal ganglion cell recordings. In addition, in some retinal ganglion cells of cats the GABA antagonist bicuculline decreases the activity of the inhibitory surround. These findings led to two predicitions: 1) benzodiazepines will selectively increase the inhibitory surround of human visual receptive fields, 2) after dark adaptation, no free GABA will be available in the synapses and benzodiazepines will have no effect on the visual system. Characteristics of human receptive fields were determined by subthreshold summation: the contrast threshold of a vertical line was measured dependent on the distance of two parallel flanking lines whose contrast was below threshold. Both hypotheses were confirmed: the threshold in the inhibitory region of receptive fields was specifically increased in a dose-dependent manner by midazolam PO (7.5 mg: P < 0.05; 15 mg: P < 0.01). In dark-adapted subjects no effect of midazolam was found. Control experiments with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed no specific effect. The visual system may be a model to bridge the gap between animal and human psychopharmacology.