Center for Behavioral Teratology, Department of Psychology, San Diego State University, San Diego, California;
Physiol Genomics. 2010 May;41(3):232-43. doi: 10.1152/physiolgenomics.00113.2009. Epub 2010 Feb 9.
Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5-15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.
酒精摄入量的增加与跨物种对甜味物质的偏好增强有关，这种现象可能是由口腔中酒精对甜味感知神经生物学基质的激活所介导的。在这里，我们通过测量 T1r3 受体缺陷型和其 C57BL/6J 背景品系小鼠对口服酒精的行为和中枢神经生理反应，直接研究了 T1r3 受体蛋白（对哺乳动物的甜味感知至关重要）对乙醇摄入和偏好以及乙醇味觉的神经处理的贡献。T1r3 敲除和野生型小鼠分别在长期自愿摄入广泛浓度范围的乙醇、蔗糖和奎宁的行为偏好测定中进行测试。对于神经生理实验，每组的小鼠用麻醉剂麻醉，并从孤束核的味觉神经元中记录对乙醇和不同味觉品质刺激的电生理味觉反应。缺乏 T1r3 受体的小鼠对酒精（即约 50%的偏好值）的行为表现无差异，而这些浓度通常是野生型小鼠所偏好的（5-15%）。与 C57BL/6J 对照组相比，T1r3 缺陷型小鼠对乙醇的中枢神经味觉反应明显较低，对于该品系，口服乙醇刺激会产生对甜味反应性 NTS 味觉神经元的浓度依赖性激活。在高于 15%的浓度下，敲除小鼠和对照小鼠之间对乙醇偏好的差异减弱表明，其他感觉和/或摄食后效应与高浓度下的甜味输入竞争。正如预期的那样，T1r3 敲除小鼠对甜味剂的行为和神经味觉反应明显受到抑制，但对典型的盐、酸或苦味刺激与野生型小鼠无差异。这些数据表明 T1r3 受体参与了乙醇味觉的感觉检测和转导。
