Circadian and acamprosate modulation of elevated ethanol drinking in mPer2 clock gene mutant mice.
Circadian and acamprosate modulation of elevated ethanol drinking in mPer2 clock gene mutant mice.
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DOI：
10.3109/07420528.2011.601968
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发表时间：
2011-10
影响因子：
2.8
通讯作者：
Glass JD
中科院分区：
文献类型：
--
作者：
Brager AJ;Prosser RA;Glass JD
Per2时钟基因调节乙醇消耗，因此不表达功能性mPer2的突变小鼠改变了昼夜节律行为，促进了更高的乙醇摄入和偏好。研究人员进行了实验，以表征mPer2缺失对乙醇摄入的昼夜相关行为影响，并探索阿坎普罗酸（用于减少酒精依赖）如何改变乙醇摄入的日模式。将雄性mPer2突变体和野生型小鼠置于12L:12D光循环中，记录其运动和饮水活动。昼夜运动测量证实，与WTs相比，mPer2突变体的夜间活动开始时间提前约2小时，夜间活动持续时间延长（p<0.01）。此外，与WTs相比，mPer2突变体更喜欢和消耗更多的乙醇，并且每天有更多的乙醇饮用事件。使用皮下微透析对全身乙醇的测量证实了mPer2突变体中乙醇摄入量的提前增加，24小时平均为~60 mM，而WTs为~25 mM （p<0.01）。为期6天的单次丙酸注射（300 mg/kg）并没有改变mPer2突变体夜间饮酒的早期发作，但降低了饮酒的总体幅度和偏好（p<0.01）。Acamprosate也降低了WTs中的这些参数。这些结果表明，mPer2突变体中乙醇摄入量升高可能是夜间活动开始时间提前和夜间饮酒活动增加的部分结果。阿坎普罗酸对乙醇摄入的抑制作用不是由于饮酒的昼夜模式改变，而是由于每日饮酒次数和每次饮酒次数的减少。
The Per2 clock gene modulates ethanol consumption, such that mutant mice not expressing functional mPer2 have altered circadian behavior that promotes higher ethanol intake and preference. Experiments were undertaken to characterize circadian-related behavioral effects of mPer2 deletion on ethanol intake and to explore how acamprosate (used to reduce alcohol dependence) alters diurnal patterns of ethanol intake. Male mPer2 mutant and WT (wild-type) mice were entrained to a 12L:12D photocycle and their locomotor and drinking activities were recorded. Circadian locomotor measurements confirmed that mPer2 mutants had an advanced onset of nocturnal activity of about 2 h relative to WTs, and an increased duration of nocturnal activity (p<0.01). Also, mPer2 mutants preferred and consumed more ethanol and had more daily ethanol drinking episodes vs. WTs. Measurements of systemic ethanol using subcutaneous microdialysis confirmed the advanced rise in ethanol intake in the mPer2 mutants, with 24 hr averages being ~60 mM vs. ~25 mM for WTs (p<0.01). A six-day regimen of single i.p. acamprosate injections (300 mg/kg) did not alter the earlier onset of nocturnal ethanol drinking in the mPer2 mutants, but reduced the overall amplitude of drinking and preference (both, p<0.01). Acamprosate also reduced these parameters in WTs. These results suggest that elevated ethanol intake in mPer2 mutants may be a partial consequence of an earlier nighttime activity onset and increase in nocturnal drinking activity. The suppressive action of acamprosate on ethanol intake is not due to an altered diurnal pattern of drinking, but rather, a decrease in the number of daily drinking bouts and drinking per bout.
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影响因子：
3.4
作者：
Comasco E;Nordquist N;Göktürk C;Aslund C;Hallman J;Oreland L;Nilsson KW
通讯作者：
Nilsson KW
影响因子：
3.3
作者：
McElroy, B.;Zakaria, A.;Glass, J. D.;Prosser, R. A.
通讯作者：
Prosser, R. A.
影响因子：
3.7
作者：
Pendergast JS;Friday RC;Yamazaki S
通讯作者：
Yamazaki S
影响因子：
2.8
作者：
Portaluppi, Francesco;Smolensky, Michael H.;Touitou, Yvan
通讯作者：
Touitou, Yvan
影响因子：
3.5
作者：
Seggio JA;Fixaris MC;Reed JD;Logan RW;Rosenwasser AM
通讯作者：
Rosenwasser AM