Reductions in retinal γ-aminobutyric acid (GABA) content and in [ ³H]flunitrazepam binding after postnatal monosodium glutamate injections in rats

Specific binding of [ ³H]flunitrazepam is found in the mammalian retina and its characteristics are similar in important respects to those in the cerebral cortex. Numerous reports have shown that monosodium glutamate (MSG) given neonatally to rats results in neuronal cell death with sparing of photoreceptor and glial cells. Sprague-Dawley rats were given MSG (3.2 mg/g i.p.) from day 2 to day 12 after birth; controls received equimolar injections of NaCl. At 8 to 9 weeks of age, the rats were killed and [ ³H]flunitrazepam binding was examined in the retinas and various brain regions. Histologic evidence showed the virtual absence of ganglion cells and a marked reduction of neurons in the inner nuclear layer of retinas from MSG-treated rats; photoreceptor and Muller cells appeared normal. In the retinas from MSG-treated rats, γ-aminobutyric acid levels were decreased by 73% and B(max) of [ ³H]flunitrazepam binding was decreased by 77%; there was no change in K(d). In the cerebellum, cerebral cortex and hypothalamus of MSG-treated rats, [ ³H]flunitrazepam binding was unchanged. These results strengthen the association of γ-aminobutyric acid mechanisms with benzodiazepine binding and suggest a predominant neuronal localization of the binding sites.