Decrease of (+)-3-[125I]MK-801 binding to NMDA brain receptors revealed at puberty in rats treated neonatally with monosodium glutamate.

Obesity, altered pattern of gonadal hormone secretion, advanced vaginal opening, irregular cycling, altered sexual behavior and infertility are the effects of the neonatal administration of monosodium glutamate (MSG) to rodents. These are the consequences of lesions located mainly in the hypothalamic region. It is believed that the receptors to N-methyl-D-aspartic acid (NMDA) actively participate in the onset and development of such lesions, on the other hand, they may be altered by neuronal dysfunction as well, seriously compromising the glutamatergic pathways that are involved in the neuroendocrine regulation. To clarify the scope of the lesion induced by MSG and its probable effects on the NMDA receptors, we measured them with a very sensitive ligand for autoradiography, (+)-3-[125I]MK-801. Coronal cuts at the level of the arcuate-median eminence of brains from 4-, 8- and 40-day-old rats treated neonatally with MSG (4 mg/g) or saline (controls) were examined. In the normal hypothalamus, NMDA receptor labelling was higher in the young animals than in the 40-day-old animals, and this was observed in both control and treated rats. NMDA receptor labelling of rats at puberty was very low, and no apparent differences were observed between groups. In contrast, in areas where an increase in NMDA binding sites normally occurs with development, a significant impairment of the normal augmentation of MK-801 binding was revealed. In the hippocampal layers, stratum radiatum and stratum oriens and in the cerebral cortex of 40-day-old rats treated with MSG a lower amount of binding was observed, of about 50% fewer sites compared to the untreated controls at the level of CA3 and in the outer layer of the parietal cortex. These results suggest that at an early stage of the MSG lesion the NMDA receptors located in the hypothalamus and other brain areas are apparently expressed normally, but at puberty the effects of the lesion are revealed in the hippocampus and cerebral cortex by a decrease in the density of binding. Thus, the abnormal neuroendocrine and behavioral responses displayed by the MSG-treated rats may be contributed partially by the alteration of the NMDA receptors in these areas.