Specific ethanol withdrawal seizures in genetically selected mice.

Specific ethanol withdrawal seizures in genetically selected mice.
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基因选择小鼠的特定乙醇戒断癫痫发作。

DOI:
10.1016/0024-3205(84)90511-3
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发表时间:
1984
期刊:
影响因子:
6.1
通讯作者:
E. Young
E. Young
中科院分区:
医学2区
文献类型:
--
作者:
J. McSwigan;J. Crabbe;E. Young

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我们正在选择性地培育易受(WSP)和耐(WSR)乙醇戒断癫痫发作的小鼠,通过处理诱导的惊厥(HIC)进行评估。检查了HIC评分的线之间的差异是一般CNS兴奋性差异的结果的可能性,而不是特定于乙醇戒断。使用产生全身性癫痫发作的治疗(电惊厥休克、士的宁和氟甲氧)和γ-氨基丁酸(GABA)拮抗剂(印防己毒素、荷包牡丹碱和戊四氮),在选定的品系中测定癫痫发作的ED 50。此外,测定了WSP和WSR小鼠对乙醇抗惊厥作用的敏感性。ECS的惊厥安培50(CA 50)和任何药物治疗的ED 50在所选品系中均无差异。当在ECS之前给予乙醇(1.5g/kg)时,在细胞系中存在显著的差异抑制:WSR小鼠的CA_(50)升高5倍,而WSP小鼠的CA_(50)仅升高2倍。乙醇预处理也使WSR小鼠士的宁和氟乙的ED_(50)显著高于WSP小鼠,但线差小于对ECS的抗惊厥作用。乙醇预处理后,WSR和WSP系之间GABA拮抗剂的ED 50没有差异。我们的结论是,遗传选择是生产线的小鼠,不同的具体程度的癫痫发作的严重程度所造成的退出乙醇的身体依赖性,而不是在广义的中枢神经系统兴奋性。乙醇对某些惊厥治疗的抗惊厥作用的敏感性增加,似乎是WSR品系中对选择的相关反应。
We are selectively breeding mice prone (WSP) and resistant (WSR) to ethanol withdrawal seizures assessed by handling induced convulsions (HIC). The possibility that differences between the lines in HIC scores are a result of differences in general CNS excitability not specific to ethanol withdrawal was examined. Using treatments which produce generalized seizures (electroconvulsive shock, strychnine, and flurothyl) and gamma amino-butyric acid (GABA) antagonists (picrotoxin, bicuculline, and pentylentetrazol), the ED50for seizures was determined in the selected lines. In addition, the sensitivity of WSP and WSR mice to the anticonvulsant actions of ethanol against each treatment was determined. Neither the convulsant amperage50(CA50) for ECS nor the ED50for any drug treatment differed for the selected lines. When ethanol (1.5 g/kg) was administered prior to ECS, there was a dramatic differential suppression of ECS in the lines: the CA50) of WSR mice was elevated 5-fold, whereas the CA50of WSP mice increased only two fold. Ethanol pretreatment also elevated the ED50for strychnine and flurothyl in WSR mice significantly more than WSP mice, but the line difference was smaller than for the anticonvulsant effect against ECS. The ED50s for the GABA antagonists were not different between the WSR and WSP lines after ethanol pretreatment. We conclude that genetic selection is producing lines of mice that differ specifically in the degree of seizure severity caused by withdrawal from ethanol physical dependence and not in generalized CNS excitability. An increased sensitivity to the anticonvulsant effects of ethanol against some convulsant treatments has appeared as a correlated response to selection in the WSR line.
DOI: --
发表时间: 1982-12
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
G. Frye;G. Breese
通讯作者: G. Frye;G. Breese
将γ-氨基丁酸(GABA)激动剂微注射到下丘、黑质或内侧隔膜后,乙醇依赖性大鼠对听源性癫痫发作的易感性特征。
DOI: --
发表时间: 1983
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
Frye,GD;McCown,TJ;Breese,GR
通讯作者: Breese,GR
大鼠乙醇戒断症状对γ-氨基丁酸(GABA)模拟物的不同敏感性:阻断听源性癫痫发作,但不阻断前肢震颤。
DOI: --
发表时间: 1983
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
Frye,GD;McCown,TJ;Breese,GR
通讯作者: Breese,GR