Boyce-Rustay Janel M, Janos Alicia L, Holmes Andrew
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
Behav Brain Res. 2008 Jan 10;186(1):133-7. doi: 10.1016/j.bbr.2007.07.031. Epub 2007 Aug 2.
There is a strong clinical relationship between stress and stress-related disorders and the incidence of alcohol abuse and alcoholism, and this relationship appears to be partly genetic in origin. There are marked strain differences in ethanol (EtOH)-related behaviors and reactivity to stress, but little investigation of the interaction between the two. The present study assessed the effects of chronic exposure to swim stress on EtOH-related behavior in three common inbred strains of mice, C57BL/6J, DBA/2J and BALB/cByJ. After establishing baseline (10%) EtOH self-administration in a two-bottle free choice test, mice were exposed to daily swim stress for 14 consecutive days and EtOH consumption was measured as a percent of baseline both during stress and for 10 days afterwards. A separate experiment examined the effects of 14 days of swim stress on sensitivity to the sedative/hypnotic effects of an acute injection of 4g/kg EtOH. Results showed that stress produced a significant decrease in EtOH consumption, relative to pre-stress baseline, in DBA/2J and BALB/cByJ, but not C57BL/6J mice. By contrast, stress increased sensitivity to the sedative/hypnotic effects of EtOH in all three strains. These findings demonstrate that chronic swim stress produces reductions in EtOH self-administration in a strain-dependent manner, and that these effects may be restricted to strains with a pre-existing aversion to EtOH. Present data also demonstrates a dissociation between effects of this stressor on EtOH self-administration and sensitivity to EtOH's sedative/hypnotic effects. In conclusion, strain differences, that are likely in large part genetic in nature, modify the effects of this stressor on EtOH's effects in a behavior-specific manner.
压力及与压力相关的疾病与酒精滥用和酒精中毒的发生率之间存在密切的临床关系,而且这种关系似乎部分源于遗传。在与乙醇(EtOH)相关的行为以及对应激的反应性方面存在显著的品系差异,但对二者之间的相互作用却鲜有研究。本研究评估了长期暴露于游泳应激对三种常见近交系小鼠(C57BL/6J、DBA/2J和BALB/cByJ)与EtOH相关行为的影响。在双瓶自由选择试验中建立基线(10%)EtOH自我给药后,小鼠连续14天每日暴露于游泳应激,应激期间及之后10天测量EtOH消耗量,并以占基线的百分比表示。另一个实验研究了14天游泳应激对急性注射4g/kg EtOH的镇静/催眠作用敏感性的影响。结果显示,相对于应激前基线,应激使DBA/2J和BALB/cByJ小鼠的EtOH消耗量显著降低,但C57BL/6J小鼠未出现此现象。相比之下,应激增加了所有三个品系对EtOH镇静/催眠作用的敏感性。这些发现表明,长期游泳应激以品系依赖的方式降低EtOH自我给药,且这些影响可能仅限于原本就厌恶EtOH的品系。目前的数据还表明,这种应激源对EtOH自我给药的影响与对EtOH镇静/催眠作用的敏感性之间存在分离。总之,很大程度上可能是遗传性质的品系差异以行为特异性方式改变了这种应激源对EtOH作用的影响。