CAJ | 학술논문

电生理研究证明,焦虑与忧郁剂治疗的神经生物学机制取决于影响特异性的解剖区域对5HT 1A受体敏感的适应性.此外,临床上用相应的抗焦虑/抗忧郁药剂重复处理,在前脑的作用表现为增进5-HT的神经传导,尤以海马最显著.药物处理2～3周后,可减少抑制性体树突自动受体的敏感性,增加突触后的受体敏感性,或两者兼备.使用对氮,氮二丙基-5-氨基色胺刺激的鸟苷-5-氧(3硫代)三磷酸盐([35S]GTPyS)结合体进行放射自显影照相的方法评估,测定了该假设.将大白鼠用生理盐水或药剂处理21d,每天处理1次(mg/kg:fluoxetine,10;imipramine,10;clorgyline,1)或每天处理2次(tpsapirone,20mg/kg).检测了3个富含5 HT1A受体的脑区:背中缝核(DR;体树突),背侧海马(DH)和外侧隔区(LS)(突触后).只有imipramine(+17%)和fluoxetine(+54%)显著地增加了背侧海马上激活剂结合在背侧海马.除了imipramine,所有药剂均减少在背侧中缝核的结合(-19到41%).尽管总的说来结果支持增进海马5-HT的神经传导的概念,但受体敏感性变化的模式与电生理的研究结果仍稍有不同.然而,最一致和最显著的结果是四种药剂处理均在外侧隔区(LS)降低[35S]GTPγS结合(14到-23%),前人在慢性的丁螺旋酮处理后也有报道,这也许是抗忧郁剂治疗至今尚无被普遍认可的结果,建议对此进一步研究.
전생리연구증명,초필여우욱제치료적신경생물학궤제취결우영향특이성적해부구역대5HT 1A수체민감적괄응성.차외,림상상용상응적항초필/항우욱약제중복처리,재전뇌적작용표현위증진5-HT적신경전도,우이해마최현저.약물처리2～3주후,가감소억제성체수돌자동수체적민감성,증가돌촉후적수체민감성,혹량자겸비.사용대담,담이병기-5-안기색알자격적조감-5-양(3류대)삼린산염([35S]GTPyS)결합체진행방사자현영조상적방법평고,측정료해가설.장대백서용생리염수혹약제처리21d,매천처리1차(mg/kg:fluoxetine,10;imipramine,10;clorgyline,1)혹매천처리2차(tpsapirone,20mg/kg).검측료3개부함5 HT1A수체적뇌구:배중봉핵(DR;체수돌),배측해마(DH)화외측격구(LS)(돌촉후).지유imipramine(+17%)화fluoxetine(+54%)현저지증가료배측해마상격활제결합재배측해마.제료imipramine,소유약제균감소재배측중봉핵적결합(-19도41%).진관총적설래결과지지증진해마5-HT적신경전도적개념,단수체민감성변화적모식여전생리적연구결과잉초유불동.연이,최일치화최현저적결과시사충약제처리균재외측격구(LS)강저[35S]GTPγS결합(14도-23%),전인재만성적정라선동처리후야유보도,저야허시항우욱제치료지금상무피보편인가적결과,건의대차진일보연구.
Electrophysiological studies have led to the proposal that the neurobiological mechanism(s) underly ing drug therapy of anxiety and depression involve (s) regionally - specific adaptations in 5 - hydrox ytryptamine1A(5- HT1A) receptor sensitivity. Furthermore, the net effect of clinically- relevant repeated treatment with anxiolytic/antidepressant drugs, regardless of chemical class, appears to reflect an enhance ment of 5 - HT neurotransmission in forebrain targets, most notably in the hippocampus. Depending on the drug utilized, a decrease in sensitivity of inhibitory somatodendritic autoreceptors, an increase in sensitivity of postsynaptic receptors, or both alterations, occurs after 2 - 3 weeks of treatment. This hypothesis was tested using N, N - dipropyl - 5 - carboxamidotryptamine (N, N DP - 5 CT) - stimulated guanosine - 5' - O (3- thio)triphosphate ([35S] GTPγS) binding assessed by autoradiography. Rats were treated for 21 days with saline or drug (in mg/kg) once (fluoxetine, 10; imipramine, 10; clorgyline, 1) or twice daily ( ip sapirone, 20) and three brain regions rich in 5 - HT1A receptors were examined: the dorsal raphe (somatoden dritic), the dorsal hippocampus (postsynaptic), and the lateral septum (postsynaptic). Only imipramine ( + 17 % ) and fluoxetine ( + 54 % ) significantly increased agonist- stimulated binding in the dorsal hippocampus; all drugs except imipramine significantly decreased binding in the dorsal raphe ( - 19 to - 41% ). Although these results generally support the concept of a net enhancement of hippocampal 5 - HT neurotransmission, the pattern of changes in receptor sensitivity differed somewhat from the results of electrophysiological studies. The most consistent effect, however, was a significant decrease in stimulated [35S]GTPγS binding in the lat eral septum after all four treatments ( 14 to 23% ), a finding previously reported also after chronic bus pirone treatment, suggesting this may be a heretofore unrecognized common outcome of antidepressant treat ment deserving further study.