NMDA and non-NMDA sensitive [ l- 3H] glutamate receptor binding in the brain of the Naples high- and low-excitability rats: an autoradiographic study

Abstract

The Naples high-excitability (NHE) and low-excitability (NLE) rat lines, selectively bred for high and low activity in a Làt maze, respectively, are used as an animal model in the study of hippocampal functions. The aim of this study was to investigate the anatomical distribution of N-methyl- d-aspartate (NMDA) and non-NMDA sensitive [ 3H]glutamate receptor binding by quantitative autoradiography in the brain of the NHE and NLE rats with a randomly bred line (NRB) as controls. Twenty-micron-thick cryostat sagittal sections were incubated at 4°C with 150 nM [ l- 3H]glutamate alone or in the presence of 100 μM NMDA or 2.5 μM quisqualate (QA). Non-specific binding was determined in the presence of 1 mM of non-labeled glutamate. The sections were exposed to tritium-sensitive films for 3 weeks at 4°C. Quantitative analysis revealed: (1) higher levels of total binding in NHE than in NRB and NLE rats in all areas but the cerebellum; (2) fewer binding sites for both NMDA and QA receptors and larger binding sites for QA receptors in the hippocampus of NLE and NHE rats, respectively; (3) a positive correlation between total binding sites and activity level in a Làt maze in all areas, except the cerebellar molecular layer with NLE < NHE, which was due to a differential contribution from NMDA and non-NMDA types. Thus, the brain of the NHE rats shows an imbalance between NMDA and non-NMDA sensitive [ l- 3H]glutamate receptors.