Comparative behavioral characterization of the neuroactive steroids 3α-OH,5α-pregnan-20-one and 3α-OH,5β-pregnan-20-one in rodents
Comparative behavioral characterization of the neuroactive steroids 3α-OH,5α-pregnan-20-one and 3α-OH,5β-pregnan-20-one in rodents
复制标题
啮齿类动物神经活性类固醇 3α-OH,5α-pregnan-20-one 和 3α-OH,5β-pregnan-20-one 的比较行为特征
作者：
S. Wieland;N. Lan;J. Belluzzi;L. Stein
孕酮类固醇已被证明具有麻醉、催眠、抗惊厥和缓解焦虑的特性。本研究采用行为学方法研究了两种内源性神经活性类固醇异构体3-α-羟基-5-α-孕烷-20-酮(3α，5α-P)和3α-羟基-5β-孕烷-20-酮3α，5β-P的药理性质。3-α、5-α-P和3-α-5-β-P对戊四氮诱导的小鼠癫痫发作的阻断作用相似(ED50：3α，5α-P=2.8 mg/kg和3α，5β-P=3.0 mg/kg)。类似地，两种神经活性类固醇在相同的效力范围内产生转杆缺陷(TD50：3α，5α-P=18.8 mg/kg和3α，5β-P=21.2 mg/kg)。然而，在焦虑的动物模型中，观察到这两种异构体之间的细微差异。在明暗转换实验和高架正迷宫实验中，3α，5β-P的药效均优于3α，5α-P，但两者效价相近。在盖勒-赛弗试验中，3α、5β-P比3α、5α-P更有效、更有效。在所测试的剂量范围内，两种化合物对不受惩罚的反应均无显著影响。这两种化合物在运动测试中产生了相似的双相曲线。结果表明，3-α、5-α-P和3-α、5-β-P具有相似的抗惊厥活性，但5-β-异构体的抗焦虑作用强于5-α-异构体。
Pregnan steroids have been shown to possess anesthetic, hypnotic, anticonvulsant and anxiolytic properties. In this study, two endogenous neuroactive steroid isomers, 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) and 3α-hydroxy-5β-pregnan-20-one 3α,5β-P), were studied for differences in their pharmacological properties using behavioral assays. 3α,5α-P and 3α,5β-P were similar in their potencies and efficacies in blocking pentylenetetrazol-induced seizures in mice (ED50: 3α,5α-P=2.8 mg/kg and 3α,5β-P=3.0 mg/kg). Similarly, both neuroactive steroids produced roto-rod deficits within the same range of potency (TD50:3α,5α-P=18.8 mg/kg and 3α,5β-P=21.2 mg/kg). However, in animal models of anxiety, subtle differences were observed between the two isomers. In both the light/dark transition test and elevated plus-maze, 3α,5β-P was more efficacious than 3α,5α-P, though both compounds had similar potencies. In the Geller-Seifter test, 3α,5β-P was more potent and efficacious than 3α,5α-P. Neither compound had significant effects on unpunished responding within the dose range tested. Both compounds produced similar biphasic curves in the locomotor test. All together, the data indicate that 3α,5α-P and 3α,5β-P have similar anticonvulsant activity, but the 5β-isomer possesses more potent and efficacious anxiolytic properties than the 5α-isomer.
大鼠额叶皮层和脊髓中的 γ-氨基丁酸 A 受体复合物对类固醇调节表现出不同的反应。
影响因子：
3.6
作者：
Gee,KW;Lan,NC
通讯作者：
Lan,NC
类固醇识别位点与表达的 GABA(A)-苯二氮卓受体功能偶联。
影响因子：
5
作者：
Lan,NC;Chen,JS;Belelli,D;Pritchett,DB;Seeburg,PH;Gee,KW
通讯作者：
Gee,KW