Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats

Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats
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DOI:
10.1006/hbeh.2002.1763
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发表时间:
2002-05-01
影响因子:
3.5
通讯作者:
Walf, AA
Walf, AA
中科院分区:
医学3区
文献类型:
--
作者:
Frye, CA;Walf, AA

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这些实验的目的是验证一种假说,即减弱海马区5α-孕酮代谢产物5α-孕酮-3α-醇-20-酮(3α,5α-THP)的内源性增加将改变发情前期大鼠的焦虑和抑郁行为。在实验1中,比较了应具有高(发情期)和低(发情期和雄性)内源性海马3α,5α-THP的大鼠的焦虑(旷场)和抑郁(强迫游泳试验)行为。与发情前期大鼠或雄性大鼠相比,发情前期大鼠表现出更多的焦虑样行为(在开阔场地中央进入增加)和抗抑郁样行为(在强迫游泳测试中表现为较少的静止)。在实验2和实验3中,分别比较了发情大鼠全身给药和海马内注射非那雄胺对开阔游泳和强迫游泳行为的影响。非那雄胺是一种5α-还原酶抑制剂,可将孕酮代谢减弱为3α,5α-THP,与赋形剂给药比较。与给药组相比,全身或海马区注射非那雄胺减少了开阔水域的中枢入射,增加了强迫游泳试验中的不动。实验四,观察全身给药和海马区注射非那雄胺与赋形剂对发情前期大鼠海马区3α、5α-THP的影响。非那雄胺,SC或海马内注射,与赋形剂给药相比,减少了海马区3Alpha,5Alpha-THP。综上所述,这些数据表明,海马区3Alpha、5Alpha-THP水平的变化可能会缓解骑自行车大鼠焦虑和抑郁行为的发育期变化。(C)2002年埃尔塞维尔科学公司(美国)。
The purpose of these experiments was to test the hypothesis that attenuating the endogenous increase of the 5alpha-reduced progesterone metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) in the hippocampus will alter anxiety and depression behavior of proestrous rats. In Experiment 1, anxiety (open field) and depression (forced swim test) behavior was compared of rats that should have high (proestrous) and low (diestrous and male rats) endogenous hippocampal 3alpha,5alpha-THP. Proestrous rats exhibited more anxiolytic-like (increased central entries in the open field) and anti-depressant-like (less immobility in the forced swim test) behavior than diestrous or male rats. In Experiments 2 and 3, respectively, systemic and intrahippocampal finasteride, a 5alpha-reductase inhibitor which attenuates progesterone's metabolism to 3alpha,5alpha-THP, versus vehicle administration to proestrous rats was compared for effects on open field and forced swim test behavior. Systemic or intrahippocampal finasteride decreased central entries in the open field and increased immobility in the forced swim tests compared to vehicle administration. In Experiment 4, the effects of systemic and intrahippocampal finasteride vs vehicle administration on hippocampal 3alpha,5alpha-THP of proestrous rats was examined. Finasteride, SC or intrahippocampally, reduced 3alpha,5alpha-THP in the hippocampus compared to vehicle administration. Together these data suggest that variations in 3alpha,5alpha-THP levels in the hippocampus may mitigate proestrous changes in anxiety and depressive behavior of cycling rats. (C) 2002 Elsevier science (USA).