Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, United States.
Behav Brain Res. 2011 Nov 20;225(1):358-62. doi: 10.1016/j.bbr.2011.07.013. Epub 2011 Jul 19.
Findings are mixed regarding the expression of tolerance after repeated ethanol exposure, perhaps in part due to dose/frequency variations in exposure regimens. The present study compared age-related differences in tolerance development following 10 days of 1g/kg twice daily, 2g/kg once daily, or intermittent 4g/kg ethanol exposure regimens. To measure expression of chronic tolerance and acute tolerance, ethanol-induced motor impairment was assessed on day 12, with functionally equivalent ethanol doses administered across age (2g/kg - adolescents; 1.5g/kg - adults). Subsequent challenge doses resulted in lower brain ethanol concentrations in both age groups as a function of the chronic ethanol regimens. Expected age-related differences emerged in acute tolerance expression in non-manipulated animals, with adolescents, but not adults showing acute tolerance. Regimens sufficient to induce alterations in ethanol metabolism did not result in chronic functional tolerance at either age, although chronic injections were sufficient to induce acute tolerance in adults.
关于反复乙醇暴露后耐受性的表达结果不一,部分原因可能是由于暴露方案中的剂量/频率变化。本研究比较了在 10 天内接受 1g/kg 每日两次、2g/kg 每日一次或间歇性 4g/kg 乙醇暴露方案后,年龄相关的耐受性发展差异。为了测量慢性和急性耐受性的表达,在第 12 天评估了乙醇诱导的运动障碍,在整个年龄组中给予等效的功能乙醇剂量(2g/kg-青少年;1.5g/kg-成年人)。随后的挑战剂量导致两个年龄组的大脑乙醇浓度降低,这是慢性乙醇方案的作用。在未经操作的动物中,急性耐受性的表达出现了预期的与年龄相关的差异,青少年表现出急性耐受性,但成年人没有。虽然慢性注射足以在成年人中引起急性耐受,但足以引起乙醇代谢改变的方案在两个年龄组均未导致慢性功能耐受。