Howells Fleur Margaret, Russell Vivienne Ann
Neuroscience Laboratory, Division of Physiology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 South Africa.
Brain Res. 2008 Mar 20;1200:107-15. doi: 10.1016/j.brainres.2008.01.033. Epub 2008 Jan 26.
Norepinephrine is known to play an integral role in different aspects of behaviour, such as attention and arousal. It has also been implicated in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). The present study was undertaken to determine the differential effects of glutamate on norepinephrine release in hippocampal slices of several rat strains. Two of the strains used in this study model behavioural disorders i.e. spontaneously hypertensive rats (SHR) mimic the behavioural characteristics of ADHD and Wistar-Kyoto (WKY) rats have been used to model depression/anxiety-like behaviours. To achieve the aims of this study, an in vitro superfusion technique was used to determine glutamate-stimulated release of radioactively labelled norepinephrine in hippocampal slices. The results show (1) SHR and Wistar rats released significantly more [(3)H]norepinephrine in response to a 1-min pulse of glutamate (1 mM) than WKY, Sprague-Dawley and Long-Evans rats. (2) Glutamate-stimulated release of [(3)H]norepinephrine was reduced by the AMPA receptor antagonist, CNQX (1 muM), suggesting that AMPA receptors are involved. (3) Exposure of hippocampal slices to a second and third 1-min pulse of glutamate revealed significant decreases in the peaks of [(3)H]norepinephrine release suggesting internalization of AMPA receptors. The rate of AMPA receptor internalization was slower in SHR than in WKY. (4) The NMDA receptor antagonist, MK-801 (10 microM) increased glutamate-stimulated release of [(3)H]norepinephrine in SHR hippocampus. This effect was blocked by CNQX, suggesting that AMPA receptors were required for the NMDA effect and that there was an NMDA component of AMPA receptor internalization in SHR hippocampus which was not evident in WKY. The present findings reveal a novel NMDA component that influences AMPA receptor-mediated regulation of norepinephrine release in SHR hippocampus.
已知去甲肾上腺素在行为的不同方面发挥着不可或缺的作用，如注意力和觉醒。它也与注意力缺陷多动障碍（ADHD）的神经生物学有关。本研究旨在确定谷氨酸对几种大鼠品系海马切片中去甲肾上腺素释放的不同影响。本研究中使用的两个品系模拟行为障碍，即自发性高血压大鼠（SHR）模拟ADHD的行为特征，而Wistar-Kyoto（WKY）大鼠则用于模拟抑郁/焦虑样行为。为实现本研究的目的，采用体外灌流技术来测定谷氨酸刺激的海马切片中放射性标记的去甲肾上腺素释放。结果表明：（1）与WKY、Sprague-Dawley和Long-Evans大鼠相比，SHR和Wistar大鼠在1 mM谷氨酸1分钟脉冲刺激下释放的[³H]去甲肾上腺素明显更多。（2）AMPA受体拮抗剂CNQX（1 μM）可降低谷氨酸刺激的[³H]去甲肾上腺素释放，表明AMPA受体参与其中。（3）海马切片暴露于第二次和第三次1分钟谷氨酸脉冲后，[³H]去甲肾上腺素释放峰值显著降低，提示AMPA受体内化。SHR中AMPA受体内化速率比WKY慢。（4）NMDA受体拮抗剂MK-801（10 μM）增加了SHR海马中谷氨酸刺激的[³H]去甲肾上腺素释放。这种作用被CNQX阻断，表明AMPA受体是NMDA作用所必需的，且SHR海马中存在AMPA受体内化的NMDA成分，而在WKY中不明显。本研究结果揭示了一种影响SHR海马中AMPA受体介导的去甲肾上腺素释放调节的新型NMDA成分。
