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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Effect of epipregnanolone and pregnenolone sulfate on chronic tolerance to ethanol.
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Effect of epipregnanolone and pregnenolone sulfate on chronic tolerance to ethanol.

机译：表孕烯醇酮和硫酸孕烯醇酮对慢性乙醇耐受性的影响。

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The aim of the present study was to investigate the influence of neurosteroids on the development of tolerance to ethanol. Male Swiss mice were injected daily with the positive allosteric modulator of the gamma amino butyric acid-A (GABA(A)) receptor epipregnanolone (5beta-pregnan-3beta-ol-20-one; 0.15 mg/kg i.p.) or pregnenolone sulfate (5-pregnen-3beta-ol-20-one sulfate sodium; 0.08 mg/kg i.p.) - considered a negative allosteric modulator of this receptor and/or positive allosteric modulator of the N-methyl-D-aspartate (NMDA) receptor - 30 min before ethanol (2.5 g/kg i.p.). They were tested on the rota-rod apparatus, under continuous acceleration (1rpm/s), at 30, 60 and 90 min after ethanol injections for 5 days. The results showed that tolerance to the motor incoordinating effect of ethanol occurred on the fifth day of treatment when this effect was blocked by pretreatment with epipregnanolone. On the other hand, ethanol tolerance was enhanced by pretreatment with pregnenolone sulfate from the second to the fifth days of treatment. Taken together, our results suggest that neurosteroids can either stimulate or block the development of chronic tolerance to ethanol. Moreover, since neurosteroids can interact with GABA(A) or NMDA receptor systems, our results suggest the involvement of these systems in the actions of neurosteroids upon ethanol tolerance.
机译：本研究的目的是研究神经甾体对乙醇耐受性发展的影响。每天向雄性瑞士小鼠注射γ-氨基丁酸-A（GABA（A））受体Epipregnanolone（5beta-pregnan-3beta-ol-20-one; 0.15 mg / kg ip）或孕烯醇酮硫酸盐的正变构调节剂。 5-pregnen-3beta-ol-20-一硫酸钠; 0.08 mg / kg ip）-被认为是该受体的阴性变构调节剂和/或N-甲基-D-天冬氨酸（NMDA）受体的阳性变构调节剂-30乙醇（2.5 g / kg ip）之前的5分钟。在乙醇注射5天后的30、60和90分钟，以连续加速（1rpm / s）在旋转棒设备上对它们进行测试。结果表明，当用乙丙孕孕酮预处理阻断了乙醇的运动协调作用后，在处理的第五天就出现了这种耐受。另一方面，从治疗的第二天到第五天用硫酸孕烯醇酮预处理可以提高乙醇耐受性。两者合计，我们的结果表明，神经固醇可以刺激或阻止对乙醇的长期耐受性的发展。此外，由于神经固醇可以与GABA（A）或NMDA受体系统相互作用，因此我们的结果表明这些系统参与了神经固醇对乙醇耐受的作用。

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