Altered glutamate binding following quinolinate lesions in developing rat brain.

To define the ontogeny of "excitotoxic" neurodegeneration further, bilateral intracerebroventricular injection of N-methyl-D-aspartate agonist, quinolinate (QUIN), was administered to rats at Postnatal Days 12, 30, and 50. Excitotoxic injury was quantified by means of changes in [3H]glutamate binding to membranes isolated from the entorhinal cortex, hippocampal formation, cerebellum, and medulla oblongata 4 days after the injection of QUIN. Binding was significantly decreased only in the hippocampal formation of 30- and 50-day-old rats (by 25 and 32%, respectively). In contrast, binding to cortical membranes was elevated by 29 and 56% at Postnatal Days 30 and 50, respectively. Observed changes in the binding of glutamate were due to modifications in the equilibrium binding constants rather than in the density of the receptors. In the cerebellum, which exhibited the highest developmental increase, the statistically significant decrease of the binding (by 36%) following QUIN lesion was only observable on Day 30. The effects of QUIN lesions were not statistically significant in the medulla oblongata. The results suggest that in 30- and 50-day-old rats QUIN can be implicated in neurodegeneration of the entorhinohippocampal complex.