Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.
Similar withdrawal severity in adolescents and adults in a rat model of alcohol dependence.
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DOI：
10.1016/j.alcohol.2009.10.017
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Nixon K
中科院分区：
文献类型：
--
作者：
Morris SA;Kelso ML;Liput DJ;Marshall SA;Nixon K
青少年时期饮酒会增加成年期出现酒精使用障碍（AUD）的风险。越来越多的证据表明，这一时期发展AUD的脆弱性增强可能是由于青少年对酒精的独特敏感性和反应。青春期大鼠对酒精中毒和戒断敏感性较低;然而，乙醇药代动力学的年龄差异可能是这些影响的基础。因此，本研究使用改良的Majchrowicz酒精依赖模型研究了酒精中毒行为和戒断严重程度，该模型已被证明尽管存在年龄差异，但血液乙醇浓度（BEC）相似。青少年（出生后，PND，35）和成年大鼠（PND 70+）接受乙醇根据这个为期四天的狂欢范式，并观察了17小时的戒断行为。正如预期的那样，青少年表现出对酒精诱导的中枢神经系统抑制的敏感性降低，表现为中毒评分显著降低。因此，相对于成人（9.2 ± 0.2 g/kg/天），青少年每天接受的乙醇（12.3 ± 0.1 g/kg/天）显著更多。尽管青春期大鼠的乙醇剂量较大，但青春期和成年组的BEC峰值相当（分别为344.5 ± 10.15 mg/dl和338.5 ± 7.8 mg/dl）。引人注目的是，青春期和成年大鼠之间的戒断严重程度在数量和质量上都相似。此外，这是第一次报告使用这种酒精依赖模型的青春期大鼠的戒断行为。第二个实验证实了在狂欢的不同时间点BEC的相似性。这些结果表明，通过使用产生相似BEC的模型考虑成人和青少年之间的乙醇药代动力学后，戒断严重程度几乎相同。这项研究，结合以前的报告，在青少年和成人的乙醇戒断，表明只有一个BEC依赖性的影响，乙醇戒断的严重程度，无论年龄。
Alcohol use during adolescence leads to increased risk of developing an alcohol use disorder (AUD) during adulthood. Converging evidence suggests that this period of enhanced vulnerability for developing an AUD may be due to the adolescent’s unique sensitivity and response to alcohol. Adolescent rats have been shown to be less sensitive to alcohol intoxication and withdrawal susceptibility; however age differences in ethanol pharmacokinetics may underlie these effects. Therefore, this study investigated alcohol intoxication behavior and withdrawal severity using a modified Majchrowicz model of alcohol dependence that has been shown to result in similar blood ethanol concentrations (BECs) despite age differences. Adolescent (postnatal day, PND, 35) and adult rats (PND 70+) received ethanol according to this four-day binge paradigm and were observed for withdrawal behavior for 17h. As expected, adolescents showed decreased sensitivity to alcohol-induced CNS depression as evidenced by significantly lower intoxication scores. Thus, adolescents received significantly more ethanol each day (12.3 ± 0.1 g/kg/day) relative to adults (9.2 ± 0.2 g/kg/day). Despite greater ethanol dosing in adolescent rats, both adolescent and adult groups had comparable peak BECs (344.5 ± 10.15 mg/dl and 338.5 ± 7.8 mg/dl respectively). Strikingly, withdrawal severity was similar quantitatively and qualitatively between adolescent and adult rats. Further, this is the first time that withdrawal behavior has been reported for adolescent rats using this model of alcohol dependence. A second experiment confirmed the similarity in BECs at various time points across the binge. These results demonstrate that after consideration of ethanol pharmacokinetics between adults and adolescents by using a model that produces similar BECs, withdrawal severity is nearly identical. This study, in combination with previous reports on ethanol withdrawal in adolescents and adults, suggests only a BEC-dependent effect of ethanol on withdrawal severity regardless of age.
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影响因子：
168.9
作者：
Hall, W;Zador, D
通讯作者：
Zador, D
DOI：
10.1097/00000374-200002000-00015
发表时间：
2000-02-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Deas, D;Riggs, P;Brown, S
通讯作者：
Brown, S
DOI：
10.1097/01.alc.0000164381.67723.76
发表时间：
2005-05-01
期刊：
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
影响因子：
--
作者：
Harford, TC;Grant, BF;Chen, CM
通讯作者：
Chen, CM
影响因子：
2.3
作者：
HUNT, WA
通讯作者：
HUNT, WA
DOI：
10.1111/j.1530-0277.1996.tb01133.x
发表时间：
1996-11-01
影响因子：
3.2
作者：
Little, PJ;Kuhn, CM;Swartzwelder, HS
通讯作者：
Swartzwelder, HS