Department of Psychology , University of North Carolina, Chapel Hill, North Carolina.
Alcohol Clin Exp Res. 2013 Oct;37(10):1688-95. doi: 10.1111/acer.12145. Epub 2013 May 3.
Recently, procedures have been developed to model specific facets of human alcohol abuse disorders, including those that model excessive binge-like drinking (i.e., "drinking-in-the-dark," or DID procedures) and excessive dependence-like drinking (i.e., intermittent ethanol [EtOH] vapor exposure). Similar neuropeptide systems modulate excessive EtOH drinking stemming from both procedures, raising the possibility that both paradigms are actually modeling the same phenotypes and triggering the same central neuroplasticity. Therefore, the goal of this present project was to study the effects of a history of binge-like EtOH drinking, using DID procedures, on phenotypes that have previously been described with procedures to model dependence-like drinking.
Male C57BL/6J mice first experienced 0 to 10 four-day binge-like drinking episodes (3 days of rest between episodes). Beginning 24 hours after the final binge-like drinking session, mice were tested for anxiety-like behaviors (with elevated plus maze [EPM] and open-field locomotor activity tests), ataxia with the rotarod test, and sensitivity to handling-induced convulsions (HICs). One week later, mice began a 40-day 2-bottle (water vs. EtOH) voluntary consumption test with concentration ranging from 10 to 20% (v/v) EtOH.
A prior history of binge-like EtOH drinking significantly increased subsequent voluntary EtOH consumption and preference, effects most robust in groups that initially experienced 6 or 10 binge-like drinking episodes and completely absent in mice that experienced 1 binge-like drinking episode. Conversely, a history of binge-like EtOH drinking did not influence anxiety-like behaviors, ataxia, or HICs.
Excessive EtOH drinking stemming from DID procedures does not initially induce phenotypes consistent with a dependence-like state. However, the subsequent increases in voluntary EtOH consumption and preference that become more robust following repeated episodes of binge-like EtOH drinking may reflect the early stages of EtOH dependence, suggesting that DID procedures may be ideal for studying the transition to EtOH dependence.
最近,人们开发了一些程序来模拟人类酗酒障碍的特定方面,包括模拟过度 binge-like 饮酒的程序(即“暗饮”或 DID 程序)和模拟过度依赖样饮酒的程序(即间歇性乙醇[EtOH]蒸气暴露)。类似的神经肽系统调节源自这两种程序的过量 EtOH 饮酒,这增加了这样一种可能性,即这两种范式实际上都在模拟相同的表型并引发相同的中枢神经可塑性。因此,本项目的目标是研究使用 DID 程序模拟 binge-like EtOH 饮酒史对先前用依赖样饮酒模拟程序描述的表型的影响。
雄性 C57BL/6J 小鼠首先经历 0 到 10 个为期 4 天的 binge-like EtOH 饮酒期(每个期之间休息 3 天)。在最后一次 binge-like 饮酒结束后 24 小时,对小鼠进行焦虑样行为(高架十字迷宫[EPM]和旷场运动活性测试)、共济失调(旋转棒测试)和对处理引起的惊厥的敏感性(HICs)测试。一周后,小鼠开始进行为期 40 天的 2 瓶(水与 EtOH)自愿消耗测试,浓度范围为 10 到 20%(v/v)EtOH。
binge-like EtOH 饮酒史显著增加了随后的自愿 EtOH 消耗和偏好,在最初经历 6 或 10 个 binge-like 饮酒期的组中效果最为显著,而在仅经历 1 个 binge-like 饮酒期的小鼠中则完全不存在。相反, binge-like EtOH 饮酒史不影响焦虑样行为、共济失调或 HICs。
源自 DID 程序的过量 EtOH 饮酒最初不会引起与依赖样状态一致的表型。然而,在经历多次 binge-like EtOH 饮酒后,自愿 EtOH 消耗和偏好的后续增加变得更加显著,这可能反映了 EtOH 依赖的早期阶段,表明 DID 程序可能是研究向 EtOH 依赖过渡的理想选择。