Silvers Janelle M, Tokunaga Sayaka, Mittleman Guy, Matthews Douglas B
University of Memphis, Memphis, Tennessee 38152, USA.
Alcohol Clin Exp Res. 2003 Oct;27(10):1606-12. doi: 10.1097/01.ALC.0000090141.66526.22.
Many humans are first exposed to ethanol during adolescence, the time at which they are most likely to binge drink ethanol. Chronic intermittent ethanol (CIE) exposure produces ethanol tolerance in adolescent rodents. Recent studies suggested that adolescent animals administered CIE experienced increased cognitive impairment following an ethanol challenge. These studies further explore development of ethanol tolerance caused by CIE in adolescence, and whether CIE during adolescence leads to altered ethanol response in adulthood.
Beginning postnatal day (P) 30, adolescent rats were administered 5.0 g/kg ethanol or saline every 48 hours for 20 days. In experiment I, animals were tested for differential weight gain. In experiment II, loss of righting reflex (LORR) was observed after each injection, then at completion of pretreatment all animals were tested with 5.0 g/kg ethanol and LORR was observed. In experiment III, blood ethanol levels were observed and elimination rates calculated after the first and fifth pretreatments. All animals were tested with 5.0 g/kg at completion of pretreatment and elimination rates were recalculated. In experiment IV, animals were trained on the spatial version of the Morris Water Maze Task (MWMT) on non-treatment days. Following completion of pretreatment and training, animals were tested after receiving an ethanol (1.0, 1.5, or 2.0 g/kg), or saline. Tests for experiments II, III, and IV were repeated in the same animals following 12 ethanol-free days.
Chronic intermittent ethanol exposure during adolescence caused differential weight gain (experiment I). Adolescent rats developed tolerance to ethanol-induced LORR (experiment II) and metabolic tolerance to ethanol (experiment III). This tolerance was seen after 12 ethanol-free days. CIE also attenuated ethanol-induced spatial memory deficits in the MWMT (experiment IV). This effect was not long-lasting.
Following CIE pretreatment during adolescence, tolerance developed to the hypnotic and cognitive impairing effects of ethanol, along with increased metabolic rate and decreased weight gain. These results further emphasize the ability of CIE to produce a variety of effects during adolescence, some having long-lasting consequences.
许多人在青春期首次接触乙醇，而这正是他们最有可能狂饮乙醇的时期。慢性间歇性乙醇（CIE）暴露会使青春期啮齿动物产生乙醇耐受性。最近的研究表明，接受CIE处理的青春期动物在乙醇激发试验后认知障碍增加。这些研究进一步探讨了青春期CIE引起的乙醇耐受性的发展，以及青春期的CIE是否会导致成年期乙醇反应改变。
从出生后第30天（P30）开始，青春期大鼠每48小时接受5.0 g/kg乙醇或生理盐水注射，持续20天。在实验I中，对动物的体重增加差异进行测试。在实验II中，每次注射后观察翻正反射消失（LORR）情况，然后在预处理完成后，所有动物均用5.0 g/kg乙醇进行测试并观察LORR。在实验III中，在第一次和第五次预处理后观察血液乙醇水平并计算消除率。预处理完成后，所有动物均用5.0 g/kg进行测试并重新计算消除率。在实验IV中，在非处理日对动物进行莫里斯水迷宫任务（MWMT）空间版本的训练。预处理和训练完成后，动物在接受乙醇（1.0、1.5或2.0 g/kg）或生理盐水后进行测试。在12个无乙醇日之后，在同一批动物中重复实验II、III和IV的测试。
青春期慢性间歇性乙醇暴露导致体重增加差异（实验I）。青春期大鼠对乙醇诱导的LORR产生耐受性（实验II），并对乙醇产生代谢耐受性（实验III）。在12个无乙醇日之后仍可见这种耐受性。CIE还减轻了MWMT中乙醇诱导的空间记忆缺陷（实验IV）。这种效果并不持久。
青春期CIE预处理后，对乙醇的催眠和认知损害作用产生了耐受性，同时代谢率增加，体重增加减少。这些结果进一步强调了CIE在青春期产生多种影响的能力，其中一些具有长期后果。
