Inagaki M, Kagaya A, Takebayashi M, Horiguchi J, Yamawaki S
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
J Neural Transm (Vienna). 1999;106(1):23-33. doi: 10.1007/s007020050138.
It has been reported that dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) is associated with affective disorders and that pathology of affective disorders are related with dysfunction of serotonin(5-HT)-2A receptor-mediated responses. In this study, we investigated the effect of DHEA on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI), 5-HT-2A receptor agonist, -induced wet dog shaking behavior (WDS) in rats. Acute treatment with DHEA inhibited the DOI-induced WDSs dose dependently. This inhibition was recovered by opioid receptor antagonist, naltrexone. 5-HT-2A receptor-mediated WDSs were desensitized after chronic treatment with DOI, however chronic treatment with DHEA had no effect on this desensitization. Chronic treatment with DHEA had no facilitating effect of chronic dexamethasone treatment on DOI-induced WDSs. These findings may lead the possibility that DHEA has the inhibitory effect of 5-HT-2A mediated signaling pathway via non-genomic action.
据报道，脱氢表雄酮（DHEA）或硫酸脱氢表雄酮（DHEA-S）与情感障碍有关，且情感障碍的病理学与5-羟色胺（5-HT）-2A受体介导反应的功能障碍相关。在本研究中，我们调查了DHEA对（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI，一种5-HT-2A受体激动剂）诱导的大鼠湿狗摇晃行为（WDS）的影响。DHEA急性处理可剂量依赖性地抑制DOI诱导的WDS。阿片受体拮抗剂纳曲酮可恢复这种抑制作用。用DOI长期处理后，5-HT-2A受体介导的WDS会脱敏，然而，DHEA长期处理对此脱敏无影响。DHEA长期处理对慢性地塞米松处理对DOI诱导的WDS无促进作用。这些发现可能提示DHEA通过非基因组作用对5-HT-2A介导的信号通路具有抑制作用。
