Terdal E S, Crabbe J C
Research Service (151W), Department of Veterans Affairs Medical Center, Portland, OR 97201.
Alcohol Clin Exp Res. 1994 Jun;18(3):542-7. doi: 10.1111/j.1530-0277.1994.tb00907.x.
Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice have been bidirectionally selected for severity of handling-induced convulsions (HIC) following withdrawal from 72 hr of chronic ethanol vapor inhalation. During selection, daily injections of the alcohol dehydrogenase inhibitor, pyrazole, were used to enhance and stabilize blood ethanol concentrations (BEC). After 26 generations of selection, WSR mice show lower withdrawal BEC than WSP mice exposed to the same ethanol vapor concentrations. Because it is desirable to compare mice maintained at the same BEC to assess correlated responses to selection, this has necessitated exposing WSR mice to higher ethanol vapor concentrations than WSP mice to achieve matched chronic BEC. The experiments reported herein demonstrate two methods for producing matched withdrawal BEC: (1) by exposing mice to the same ethanol vapor concentration and varying the pyrazole dose; and (2) by administering only ethanol at different vapor concentrations and selecting some mice with approximately the same BEC. When exposed to the same ethanol vapor concentration, WSR mice given 1.0 mmol/kg pyrazole had withdrawal BEC equivalent to WSP mice given 0.75 mmol/kg pyrazole. However, WSP mice had much more severe withdrawal HIC than WSR mice. WSP and WSR mice metabolized ethanol at the same rate following withdrawal. The basis for the differential effectiveness of pyrazole is unknown. We also exposed mice to higher ethanol vapor concentrations in the absence of pyrazole. By exposing WSR mice to higher concentrations than WSP, roughly equivalent BEC on withdrawal was achieved. Because BEC are more variable in the absence of pyrazole, it was necessary to select animals of each genotype to achieve relatively matched BEC.(ABSTRACT TRUNCATED AT 250 WORDS)
对撤药惊厥易感性（WSP）和抗性（WSR）小鼠进行了双向选择，以研究其在慢性乙醇蒸汽吸入72小时后撤药时处理诱导惊厥（HIC）的严重程度。在选择过程中，每日注射乙醇脱氢酶抑制剂吡唑以提高和稳定血液乙醇浓度（BEC）。经过26代选择后，WSR小鼠撤药时的BEC低于暴露于相同乙醇蒸汽浓度的WSP小鼠。由于需要比较维持在相同BEC水平的小鼠以评估对选择的相关反应，这就需要让WSR小鼠暴露于比WSP小鼠更高的乙醇蒸汽浓度下，以实现匹配的慢性BEC。本文报道的实验展示了两种产生匹配撤药BEC的方法：（1）将小鼠暴露于相同的乙醇蒸汽浓度并改变吡唑剂量；（2）在不同蒸汽浓度下仅给予乙醇，并选择一些BEC大致相同的小鼠。当暴露于相同的乙醇蒸汽浓度时，给予1.0 mmol/kg吡唑的WSR小鼠撤药时的BEC与给予0.75 mmol/kg吡唑的WSP小鼠相当。然而，WSP小鼠撤药时的HIC比WSR小鼠严重得多。撤药后，WSP和WSR小鼠代谢乙醇的速率相同。吡唑效果差异的基础尚不清楚。我们还在无吡唑的情况下让小鼠暴露于更高的乙醇蒸汽浓度。通过让WSR小鼠暴露于比WSP更高的浓度下，撤药时实现了大致相当的BEC。由于在无吡唑时BEC更具变异性，因此有必要选择每种基因型的动物以实现相对匹配的BEC。（摘要截短至250字）
