Prolonged corticosterone treatment alters the responsiveness of 5-HT1A receptors to 8-OH-DPAT in rat CA1 hippocampal neurons
Prolonged corticosterone treatment alters the responsiveness of 5-HT1A receptors to 8-OH-DPAT in rat CA1 hippocampal neurons
复制标题
DOI：
10.1007/s00210-002-0586-2
复制
发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Wedzony, K
中科院分区：
文献类型：
--
作者：
Czyrak, A;Mackowiak, M;Wedzony, K
在多种动物实验中，海马5-HT1A受体被糖皮质激素抑制，但其分子机制和功能意义尚不清楚。本研究旨在探讨皮质酮（10 mg/kg s.c.，每天两次，连续7天）反复给药对海马体切片电生理测量的5-HT1A受体刺激的功能影响。此外，我们还研究了皮质酮对海马5-HT1A受体结合和受体mRNA水平的影响。用皮质酮减毒(+/-)-8-羟基-2-二n -丙胺)氢溴化四氢化萘（8-OH-DPAT）长期治疗，但不是急性治疗，可诱导种群峰值抑制，并诱导大鼠CA1海马神经元的超极化。慢性而非急性皮质酮治疗也降低了CA1区域（仅在腹侧）和齿状回的5-HT1A受体结合。单剂量皮质酮增加齿状回和海马CA3和CA4区的[H-3]8-OHDPAT结合。皮质酮仅在急性期（而非长期）降低海马CA1区和齿状回5-HT1A受体mRNA水平。海马5-羟色胺的转换不受慢性皮质酮的影响。我们得出结论，长期升高的皮质酮水平可诱导海马CA1区5-HT1A受体的功能脱敏，尽管这种作用并不总是伴随着该区域或海马其他区域5-HT1A受体合成的减少。
Hippocampal 5-HT1A receptors have been shown to be suppressed by glucocorticoids in a variety of animal studies, however the molecular mechanism and the functional meaning of this effect are still not well understood.The present study was designed to investigate the impact of repeated administration of corticosterone (10 mg/kg s.c. twice daily for 7 days) on the functional consequences of 5-HT1A receptor stimulation measured electrophysiologically in hippocampal slices. Additionally, the effects of corticosterone on 5-HT1A receptor binding and on receptor mRNA levels in the hippocampus were studied. Prolonged, but not acute treatment with corticosterone attenuated (+/-)-8-hydroxy-2-di-N-propylamino)tetralin hydrobromide (8-OH-DPAT)-induced inhibition of population spikes, and 8-OH-DPAT induced hyperpolarization in rat CA1 hippocampal neurons. Chronic, but not acute treatment with corticosterone also decreased 5-HT1A receptor binding in the CA1 region (in the ventral part only) and the dentate gyrus. A single dose of corticosterone increased [H-3]8-OHDPAT binding in the dentate gyrus and in the CA3 and CA4 hippocampal regions. Only acute, but not prolonged treatment with corticosterone decreased the level of 5-HT1A receptor mRNA in the CA1 region and dentate gyrus of the hippocampus. 5-HT turnover in the hippocampus was not influenced by chronic corticosterone.It is concluded that a chronically elevated level of corticosterone can induce functional desensitization of 5-HT1A receptors in the CA1 area of the hippocampus, although this effect is not always followed consequently by decreases in 5-HT1A receptor synthesis in this or other areas of the hippocampus.