Benzodiazepines and the mammalian retina. II. Actions on retinal ganglion cells.

The effects of intravenously and iontophoretically applied benzodiazepines, midazolam and flurazepam and their receptor antagonist, flumazepil (RO 15 1788), on visually evoked and spontaneous activities of the mammalian retinal ganglion cells have been studied. Intravenously applied midazolam and flurazepam suppressed both light-evoked and spontaneous firing of rat optic tract fibres. They reduced both the sensitivity to light and the temporal resolution of the fibres. Flumazepil (RO-15-1788), on the other hand, enhanced both light-evoked and spontaneous firing of the optic tract fibres. It increased their light sensitivity but did not affect their temporal resolution. In the cat, iontophoretically applied benzodiazepines suppressed and flumazepil increased the receptive field centre and surround response as well as the spontaneous firing of ON-type retinal ganglion cells which mainly receive GABAergic inputs. However, these drugs did not affect the activities of the OFF-type cells which mainly receive glycinergic inputs. These results suggest not only that the action of benzodiazepines on the retinal ganglion cells is mediated by benzodiazepine receptors that are linked with GABA receptors, but also that the retinal benzodiazepine receptors receive an endogenous benzodiazepine receptor ligand.