Schroeder H, Becker A, Grecksch G, Schroeder U, Hoellt V
Institute of Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke-University, D-39120-, Magdeburg, Leipziger Str. 44, Germany.
Brain Res. 1998 Nov 16;811(1-2):40-6. doi: 10.1016/s0006-8993(98)00929-9.
Endogenous opioids modulate processes of central excitability such as long-term potentiation and electrical kindling. Little is known about the neurochemical alterations in the interaction of the glutamatergic and opioid system in the development of pentylenetetrazol (PTZ) kindling in rats. Therefore, in the present study we investigated glutamate, DAMGO and naltrindole receptor binding, receptor protein expression by Western blot and ex vivo glutamate transmitter release in PTZ kindled rats. The specific 3H-DAMGO and -naltrindole binding to hippocampal membranes displayed no significant changes in kindled rats compared to controls. In contrast, the 3H-l-glutamate binding was significantly enhanced after completion of PTZ kindling. The expression of receptor protein for glutamate as well as the naloxone- and naltrindole-induced 3H-d-aspartate release from hippocampal slices did not alter in any case as a consequence of PTZ kindling. The PTZ induced enhancement of the glutamate binding sites in the hippocampus was downregulated to control level by natrindole treatment of rats prior to each PTZ application. Furthermore, naltrindole pretreatment of rats significantly inhibited the development of seizure susceptibility. In contrast, naloxone was not able to alter the seizure activity induced by PTZ as well as the transmitter receptor binding. The results are discussed in the light of a modulating role of delta-opioid receptors in PTZ kindling.
内源性阿片肽调节中枢兴奋性过程，如长时程增强和电点燃。关于大鼠戊四氮（PTZ）点燃过程中谷氨酸能系统与阿片系统相互作用时的神经化学变化，目前所知甚少。因此，在本研究中，我们调查了PTZ点燃大鼠的谷氨酸、DAMGO和纳曲吲哚受体结合、通过蛋白质印迹法检测的受体蛋白表达以及离体谷氨酸递质释放情况。与对照组相比，点燃大鼠海马膜上特异性的3H-DAMGO和3H-纳曲吲哚结合没有显著变化。相反，PTZ点燃完成后，3H-L-谷氨酸结合显著增强。PTZ点燃并未导致谷氨酸受体蛋白表达以及纳洛酮和纳曲吲哚诱导的海马切片3H-D-天冬氨酸释放发生任何改变。在每次给予PTZ之前用纳曲吲哚处理大鼠，可使PTZ诱导的海马谷氨酸结合位点增强下调至对照水平。此外，大鼠纳曲吲哚预处理显著抑制癫痫易感性的发展。相反，纳洛酮不能改变PTZ诱导的癫痫活动以及递质受体结合。根据δ-阿片受体在PTZ点燃中的调节作用对结果进行了讨论。
