Translational Center for the Neurobehavioral Study on Alcohol, Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Addict Biol. 2012 Jan;17(1):121-31. doi: 10.1111/j.1369-1600.2010.00260.x. Epub 2010 Nov 4.
Voluntary oral ethanol consumption in rodents is generally limited by strong taste-aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly 'fading' away the sweetener. While useful in most instances, this approach has not proven as successful for some inbred strains of mice (e.g. DBA/2J) despite consistent evidence in the literature that these same strains express strong conditioned place preference for intraperitoneal- or intragastric-administered ethanol. Importantly, DBA/2J mice express a polymorphism in a 'sweet' taste receptor subunit gene that reduces the potency of sweet substances in these mice. We hypothesized that the presence of this polymorphism might help explain the contrasting behavioral findings of weak voluntary oral ethanol consumption following sucrose-fade yet robust conditioned place preference for ethanol in this strain. To test this, we compared ethanol consumption initiated by either a 'traditional' sucrose-fade or a fade from an alternative tastant, monosodium glutamate (MSG). We found that in both C57BL/6J and DBA/2J mice, the MSG-fade produced robust increases in home cage ethanol consumption relative to the traditional sucrose-fade. This increased ethanol intake following MSG-fade was evident across a range of ethanol concentrations. Our findings suggest the potential utility of the MSG-fade to establish stable voluntary oral ethanol consumption in mice, particularly ethanol 'non-preferring' strains such as DBA/2J and lend additional support to the notion that ethanol consumption in DBA/2J mice is limited by pronounced taste aversion.
啮齿动物通常会因为对乙醇强烈的味觉厌恶而限制自愿口服摄入乙醇。从历史上看,这一问题通过将乙醇与甜味剂(通常是蔗糖或糖精)结合来克服,然后逐渐去除甜味剂。虽然在大多数情况下这种方法很有效,但对于某些近交系小鼠(例如 DBA/2J)来说,这种方法并不成功,尽管文献中有大量证据表明这些相同的品系对腹腔内或胃内给予的乙醇表现出强烈的条件性位置偏好。重要的是,DBA/2J 小鼠在“甜”味觉受体亚基基因中存在一种多态性,这降低了这些小鼠中甜味物质的效力。我们假设这种多态性的存在可能有助于解释在该品系中,尽管蔗糖消退后自愿口服摄入乙醇的能力较弱,但对乙醇的条件性位置偏好却很强的相反行为发现。为了验证这一点,我们比较了由“传统”蔗糖消退或替代味觉物质谷氨酸单钠(MSG)消退引发的乙醇消耗。我们发现,在 C57BL/6J 和 DBA/2J 小鼠中,与传统的蔗糖消退相比,MSG 消退均会显著增加笼内乙醇消耗。这种 MSG 消退后乙醇摄入量的增加在一系列乙醇浓度下都很明显。我们的发现表明,MSG 消退在建立稳定的自愿口服乙醇摄入方面具有潜在的应用价值,特别是对于 DBA/2J 等乙醇“非偏好”品系,并进一步支持 DBA/2J 小鼠中乙醇消耗受明显味觉厌恶限制的观点。