Anxiolytic effects of the neuroactive steroid pregnanolone (3α-OH-5β-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum
Anxiolytic effects of the neuroactive steroid pregnanolone (3α-OH-5β-pregnan-20-one) after microinjection in the dorsal hippocampus and lateral septum
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DOI：
10.1016/s0006-8993(99)02150-2
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发表时间：
1999-12-11
期刊：
影响因子：
2.9
通讯作者：
Foley, M
中科院分区：
文献类型：
--
作者：
Bitran, D;Dugan, M;Foley, M
将神经活性类固醇 3 α-OH-5 beta-pregnan-20-one（孕酮）注射到成年雄性大鼠的背侧海马或侧隔后，测定其抗焦虑作用。在海马中使用 2.5 和 5 μg 孕烯醇酮后，发现在高架十字迷宫张开臂上花费的时间比例有所增加，但在侧隔膜中则没有。海马内注射 2.5 μg 孕烯醇酮 3 β-差向异构体不会影响十字迷宫中的行为； 5μg的更高剂量产生了致焦虑作用。在冲击探针埋藏试验中，海马内或间隔内注射 2.5 和 5 μg 孕烯醇酮可增加埋藏行为的潜伏期。在背侧海马或侧隔处注射孕烯醇酮0.5、2.5和5μg，埋藏行为的持续时间缩短。与冲击探针的接触次数不受颅内注射部位任何剂量的孕烯醇酮的影响。海马内或间隔内注射孕烯醇酮的抗焦虑作用可通过颅内预处理用 20 ng 印防己毒素阻断，但不能通过显微注射 5 μg 氟马西尼或 200 ng PK 11195 阻断。因此，孕烯醇酮对 GABA(A) 受体的作用介导的海马抑制作用产生了普遍的抗焦虑作用。效果。然而，侧隔膜中的类似抑制会减弱对致焦虑刺激的主动回避（即，减少埋葬行为），但不会减弱对厌恶刺激的被动回避（即，探索十字迷宫的张开臂和探针埋入测试中的电击次数）。 (C) 1999 Elsevier Science B.V. 保留所有权利。
The anxiolytic effects of the neuroactive steroid, 3 alpha-OH-5 beta-pregnan-20-one (pregnanolone), were determined after injection into the dorsal hippocampus or lateral septum in adult male rats. An increase in the proportion of time spent on the open arms of the elevated plus-maze was found after 2.5 and 5 mu g of pregnanolone in the hippocampus, but not in the lateral septum. Intrahippocampal injection of 2.5 mu g of the 3 beta-epimer of pregnanolone did not affect behavior in the plus-maze; a higher dose of 5 mu g produced an anxiogenic effect. In the shock-probe burying test latency to burying behavior was increased by intrahippocampal or intraseptal injection of 2.5 and 5 mu g of pregnanolone; the duration of burying behavior was decreased by 0.5, 2.5 and 5 mu g of pregnanolone injection in the dorsal hippocampus or lateral septum. The number of contacts with the shock probe was not affected by any dose of pregnanolone in either intracranial site of injection. The anxiolytic effects of intrahippocampal or intraseptal injection of pregnanolone were blocked by intracranial pretreatment with 20 ng of picrotoxin, but not by microinjection of 5 mu g of flumazenil or 200 ng of PK 11195. Thus, inhibition of the hippocampus, mediated by the pregnanolone's action at the GABA(A) receptor, produces a general anxiolytic effect. However, similar inhibition in the lateral septum attenuates active avoidance of anxiogenic stimuli (i.e., decreased burying behavior), but not passive avoidance of aversive stimuli (i.e., exploration of open arms of the plus-maze and number of shocks in the probe burying test). (C) 1999 Elsevier Science B.V. All rights reserved.