The impact of gonadectomy and adrenalectomy on acute withdrawal severity in male and female C57BL/6J and DBA/2J mice following a single high dose of ethanol
The impact of gonadectomy and adrenalectomy on acute withdrawal severity in male and female C57BL/6J and DBA/2J mice following a single high dose of ethanol
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DOI：
10.1111/j.1530-0277.2007.00509.x
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发表时间：
2007-11-01
影响因子：
3.2
通讯作者：
Finn, Deborah A.
中科院分区：
文献类型：
--
作者：
Gililland, Katherine R.;Finn, Deborah A.
背景：类固醇激素可以通过基因组和非基因组机制影响神经元兴奋性和随后的癫痫易感性。例如，有促惊厥类固醇如雌二醇和皮质酮和抗惊厥类固醇如睾酮、孕酮及其GABA能代谢物。最近的研究结果表明，单次急性给予乙醇会增加GABA能类固醇的水平，这种增加的来源是外周器官，如肾上腺和性腺。因此，本研究的目的是确定去除肾上腺和/或性腺对戒断严重程度的影响后，一个单一的高剂量的乙醇在2个基因型，不同的乙醇戒断severity.Method：雄性和雌性C57 BL/6 J（B6）和DBA/2 J（D2）小鼠要么保持完整（SHAM），肾上腺切除（ADX），gonadectomized（GDX），或进行ADX/GDX手术。手术后7天，在给予4 g/kg剂量的乙醇之前测量基线处理诱导的惊厥（HIC）。在乙醇注射后，然后每小时持续12小时和在24小时评估HIC。一个单独的一组小鼠被用来测量乙醇代谢的影响，在30，60，120，和240分钟后，一个单一的4克/千克剂量的ethanol.Results：ADX和ADX/GDX治疗的雄性B6和D2小鼠增加乙醇戒断严重性后，单剂量的乙醇，测定的面积下的撤退曲线和峰值HIC分数。急性乙醇戒断也增加了雌性D2小鼠，经历了ADX/GDX。相比之下，手术状态并没有改变乙醇戒断的严重程度，在雌性B6小鼠。手术状态只有轻微的影响，乙醇metabolis.Conclusions：去除外周衍生的类固醇抗惊厥性能显着增加HIC分数在急性乙醇戒断后，单剂量的乙醇在男性和女性D2小鼠和男性B6小鼠。这些增加不是由于乙醇代谢的变化。
Background: Steroid hormones can influence neuronal excitability and subsequent seizure susceptibility through genomic and nongenomic mechanisms. For example, there are proconvulsant steroids such as estradiol and corticosterone and anticonvulsant steroids such as testosterone, progesterone, and their GABAergic metabolites. Recent findings indicated that a single, acute administration of ethanol increased levels of GABAergic steroids and that the source of this increase was peripheral organs such as the adrenals and gonads. Thus, the purpose of the present study was to determine the impact of removal of the adrenals and/or gonads on withdrawal severity following a single high dose of ethanol in 2 genotypes that differ in ethanol withdrawal severity.Method: Male and female C57BL/6J (B6) and DBA/2J (D2) mice were either left intact (SHAM), adrenalectomized (ADX), gonadectomized (GDX), or underwent ADX/GDX surgery. Seven days following surgery, baseline handling-induced convulsions (HICs) were measured prior to administration of a 4 g/kg dose of ethanol. HICs were assessed following the ethanol injection, then hourly for 12 hours and at 24 hours. A separate group of mice were used to measure the impact of surgical status on ethanol metabolism at 30, 60, 120, and 240 minutes after a single 4 g/kg dose of ethanol.Results: ADX and ADX/GDX treatments in male B6 and D2 mice increased ethanol withdrawal severity following a single dose of ethanol, measured by area under the withdrawal curve and peak HIC scores. Acute ethanol withdrawal also was increased in female D2 mice that had undergone ADX/GDX. In contrast, surgical status did not alter ethanol withdrawal severity in female B6 mice. Surgical status had only minor effects on ethanol metabolism.Conclusions: Removal of peripherally derived steroids with anticonvulsant properties significantly increased HIC scores during acute ethanol withdrawal following a single dose of ethanol in male and female D2 mice and in male B6 mice. These increases were not due to changes in ethanol metabolism.