Cagnotto A, Crespi D, Mancini L, Manzoni C, Presti M L, Gariboldi M, Vezzani A, Mennini T
Laboratory of Receptor Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Neurochem. 1998 Feb;70(2):850-7. doi: 10.1046/j.1471-4159.1998.70020850.x.
We examined the effect of kindling on serotonergic neurotransmission in the hippocampus by measuring serotonin (5-HT) release and uptake in hippocampal synaptosomes and 5-HT1A and 5-HT4 receptor subtypes during and at different times after electrical kindling of the dentate gyrus. Using quantitative receptor autoradiography, we found that binding of 8-[3H]hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors was selectively increased by 20% on average (p < 0.05) in the dentate gyrus of the stimulated and contralateral hippocampus 2 days after stage 2 (stereotypes and occasional retraction of a forelimb) and by 100% on average (p < 0.05) 1 week after stage 5 (tonic-clonic seizures) compared with sham-stimulated rats. A 20% increase (p < 0.05) was observed 1 month after the last generalized seizure. No changes were found after a single afterdischarge. 5-HT4 receptors, which colocalize with 5-HT1A receptors on hippocampal neurons, were not modified in kindled tissue. [3H]5-HT uptake and its release as well as the 5-HT1B autoreceptor function did not differ from shams in hippocampal synaptosomes at stages 2 and 5. Systemic administration of 100 and 1,000 microg kg(-1) 8-OH-DPAT or 1,000 microg kg(-1) WAY-100,635, 30 min before each electrical stimulation, did not significantly alter kindling progression or the occurrence of stage 5 seizures in fully kindled rats. The changes in 5-HT1A receptor density in the dentate gyrus are part of the plastic modifications occurring during kindling and may contribute to modulating tissue hyperexcitability.
我们通过测量海马突触体中5-羟色胺（5-HT）的释放和摄取以及在齿状回电点燃期间和之后不同时间的5-HT1A和5-HT4受体亚型，研究了点燃对海马中5-羟色胺能神经传递的影响。使用定量受体放射自显影术，我们发现，与假刺激大鼠相比，在第2阶段（刻板行为和偶尔的前肢回缩）后2天，受刺激海马和对侧海马齿状回中，8-[3H]羟基-2-（二正丙基氨基）四氢萘（[3H]8-OH-DPAT）与5-HT1A受体的结合平均选择性增加20%（p<0.05）；在第5阶段（强直-阵挛性癫痫发作）后1周，平均增加100%（p<0.05）。在最后一次全身性癫痫发作后1个月观察到增加20%（p<0.05）。单次放电后未发现变化。与5-HT1A受体共定位于海马神经元上的5-HT4受体，在点燃组织中未发生改变。在第2和第5阶段，海马突触体中[3H]5-HT的摄取、释放以及5-HT1B自身受体功能与假刺激组无差异。在每次电刺激前30分钟，对完全点燃的大鼠全身给予100和1000μg kg(-1)的8-OH-DPAT或1000μg kg(-1)的WAY-100,635，并未显著改变点燃进程或第5阶段癫痫发作的发生。齿状回中5-HT1A受体密度的变化是点燃过程中发生的可塑性改变的一部分，可能有助于调节组织的过度兴奋性。
