Sadile A G, Pellicano M P, Sagvolden T, Sergeant J A
Department of Human Physiology F. Bottazzi, Second University of Naples (SUN), Italy.
Behav Brain Res. 1996 Aug;78(2):163-74. doi: 10.1016/0166-4328(95)00244-8.
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 degrees C with 150 nM [L-3H]glutamate alone or in the presence of 100 microM NMDA or 2.5 microM 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 degrees 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 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.
那不勒斯高兴奋性(NHE)和低兴奋性(NLE)大鼠品系,分别在拉什迷宫中因高活动度和低活动度而被选择性培育,被用作海马功能研究的动物模型。本研究的目的是通过定量放射自显影法,以随机繁殖品系(NRB)作为对照,研究NHE和NLE大鼠脑中N-甲基-D-天冬氨酸(NMDA)和非NMDA敏感的[3H]谷氨酸受体结合的解剖分布。将20微米厚的低温恒温矢状切片在4℃下单独与150 nM [L-3H]谷氨酸孵育,或在100 μM NMDA或2.5 μM喹啉酸(QA)存在的情况下孵育。在1 mM未标记谷氨酸存在的情况下测定非特异性结合。切片在4℃下与氚敏感膜接触3周。定量分析显示:(1)除小脑外,所有区域中NHE大鼠的总结合水平均高于NRB和NLE大鼠;(2)NLE和NHE大鼠海马中NMDA和QA受体的结合位点较少,而QA受体的结合位点较大;(3)除小脑分子层外,所有区域中总结合位点与拉什迷宫中的活动水平呈正相关,其中NLE < NHE,这是由于NMDA和非NMDA类型的不同贡献所致。因此,NHE大鼠的大脑显示出NMDA和非NMDA敏感的[L-3H]谷氨酸受体之间的失衡。