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首页> 外文期刊>Psychopharmacology >Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat.
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Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat.

机译：海马中外周线粒体苯并二氮杂receptor受体的激活刺激了异戊烷醇酮的合成并在大鼠中产生了抗焦虑作用。

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RATIONALE AND OBJECTIVES: Stimulation of the mitochondrial benzodiazepine receptor (MBR) in the brain activates the synthesis of neurosteroids that can act as positive modulators of the GABA(A) receptor complex. Allopregnanolone is a potent anxiolytic, anticonvulsant, sedative and hypnotic GABAergic neurosteroid. The anxiolytic-like effects of FGIN 1-27, an MBR agonist, were determined after microinjection into the dorsal hippocampus. METHODS: Behavior in the elevated plus-maze was assessed in adult male rats after bilateral injections of 0, 1.25, 2.5, or 5 microg FGIN 1-27. The behavioral effects of FGIN 1-27 were also determined in animals receiving intrahippocampal co-administration of 20 ng picrotoxin, 5 microg flumazenil, or 200 ng PK 11195. The effects of FGIN 1-27 on behavior in the elevated plus-maze and shock-probe burying test were measured in animals pretreated systemically with 10 mg/kg 4-MA, a 5alpha-reductase inhibitor. Hippocampal and blood plasma levels of allopregnanolone were measured in separate groups of animals pretreated with 4-MA and receiving an intrahippocampal injection of FGIN 1-27. RESULTS: Intrahippocampal injections of FGIN 1-27 produced anxiolytic-like effects in the plus-maze and in the shock-probe burying test. Hippocampal and blood levels of allopregnanolone were also increased by FGIN 1-27. The anxiolytic-like effects of FGIN 1-27 were attenuated by PK 11195 and were blocked by picrotoxin and 4-MA pretreatment, but remained unaffected by flumazenil pretreatment. The neurosteroidogenic effect of FGIN 1-27 was also eliminated by 4-MA. CONCLUSION: Activation of the MBR in the hippocampus leads to the synthesis of allopregnanolone, an anxiolytic neurosteroid that potentiates GABA(A) receptor function.
机译：理由和目的：刺激大脑中的线粒体苯并二氮杂receptor受体（MBR）可以激活神经甾体的合成，该甾体可以作为GABA（A）受体复合物的正调节剂。异戊烷醇酮是一种有效的抗焦虑，抗惊厥，镇静和催眠的GABA能神经甾体。在向海马背侧显微注射后，测定了MBR激动剂FGIN 1-27的抗焦虑作用。方法：评估成年雄性大鼠双侧注射0、1.25、2.5或5 microg FGIN 1-27后高迷宫行为。 FGIN 1-27的行为作用也已在接受海马内联合施用20 ng皮毒素，5 microg氟马西尼或200 ng PK 11195的动物中确定。FGIN1-27对高迷宫和休克行为的影响在用10 mg / kg 4-MA（一种5α-还原酶抑制剂）进行系统预处理的动物中，进行了探针掩埋试验。在分别用4-MA预处理并接受海马内注射FGIN 1-27的动物的不同组中测量了阿洛帕那诺酮的海马和血浆水平。结果：海马海马注射FGIN 1-27在正迷宫和震动探针掩埋试验中产生了类似抗焦虑的作用。 FGIN 1-27也可提高海洛因和阿洛培那那龙的血药浓度。 FGIN 1-27的抗焦虑样作用被PK 11195减弱，并被微毒素和4-MA预处理所阻断，但未受到氟马西尼预处理的影响。 FGIN 1-27的神经甾体生成作用也被4-MA消除。结论：海马区MBR的激活导致了Allopregnanolone的合成，这是一种能够增强GABA（A）受体功能的抗焦虑类固醇。

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