Schwandt Melanie L, Higley James D, Suomi Stephen J, Heilig Markus, Barr Christina S
Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center Poolesville, Maryland 20837-0529, USA.
Alcohol Clin Exp Res. 2008 Jul;32(7):1217-28. doi: 10.1111/j.1530-0277.2008.00676.x.
Acute and chronic tolerance, as well as locomotor sensitization, have been linked to ethanol intake. This study examined the change in response between 2 acutely administered doses of ethanol in adolescent rhesus macaques, with the objective of investigating rapid tolerance and locomotor sensitization to the behavioral effects of ethanol, and whether these phenomena are related to voluntary ethanol consumption in nonhuman primates.
Rhesus macaques (n = 109, 42 males, 67 females) were administered 2 sequential intravenous doses of ethanol (2.2 g/kg for males, 2.0 g/kg for females) separated by a period of 5 to 30 days. Following each injection, subjects underwent a 30-minute behavior assessment. Behavioral data were summarized using factor analysis, and compared between the 2 doses using repeated measures ANOVA. The relationship between behavioral response measures and the number of days between doses was analyzed using regression analyses. Following the second ethanol dose, subjects were given free access to an aspartame-sweetened 8.4% ethanol solution for 1 hour a day for 4 weeks. Percent change in behavioral response measures from dose 1 to dose 2 was analyzed for associations with ethanol consumption using multiple regression analyses.
Factor analysis yielded 3 factors: ataxia, stimulation, and jumping. From dose 1 to dose 2 there was a significant decrease in ataxia and a significant increase in stimulation. Peak blood ethanol concentration did not differ between doses. There were no significant associations between the number of days between doses and the magnitude of change in response for any of the behavioral measures. Percent change in stimulation from dose 1 to dose 2 was positively associated with subsequent oral ethanol consumption only in females tested in a social setting.
Adolescent rhesus macaques develop rapid tolerance to the motor-impairing effects of alcohol, while at the same time developing locomotor sensitization. These changes in response are not necessarily short lived, and may persist for some time following the first ethanol dose. Clear and consistent associations between rapid tolerance and locomotor sensitization and ethanol intake levels have yet to be demonstrated, however.
急性和慢性耐受性以及运动致敏与乙醇摄入有关。本研究检测了青春期恒河猴两次急性给予乙醇剂量后的反应变化，目的是研究对乙醇行为效应的快速耐受性和运动致敏，以及这些现象是否与非人灵长类动物的自愿乙醇消耗有关。
恒河猴（n = 109，42只雄性，67只雌性）先后静脉注射两次乙醇（雄性2.2 g/kg，雌性2.0 g/kg），间隔5至30天。每次注射后，对受试者进行30分钟的行为评估。行为数据采用因子分析进行总结，并使用重复测量方差分析比较两次剂量之间的差异。使用回归分析分析行为反应测量值与两次剂量之间天数的关系。在第二次乙醇剂量后，让受试者每天自由饮用含阿斯巴甜的8.4%乙醇溶液1小时，持续4周。使用多元回归分析分析从剂量1到剂量2行为反应测量值的百分比变化与乙醇消耗的相关性。
因子分析产生3个因子：共济失调、兴奋和跳跃。从剂量1到剂量2，共济失调显著降低，兴奋显著增加。两次剂量之间的峰值血乙醇浓度没有差异。对于任何行为测量，两次剂量之间的天数与反应变化幅度之间均无显著相关性。仅在社交环境中测试的雌性中，从剂量1到剂量2兴奋的百分比变化与随后的口服乙醇消耗呈正相关。
青春期恒河猴对酒精的运动损害作用产生快速耐受性，同时出现运动致敏。这些反应变化不一定是短暂的，可能在首次乙醇剂量后持续一段时间。然而，快速耐受性和运动致敏与乙醇摄入水平之间尚未明确且一致地证明存在关联。
