Kudelska M M, Lewis A, Ng C T, Doyle D A, Holden-Dye L, O'Connor V M, Walker R J
Biological Sciences, University of Southampton, Life Sciences Building 85, Southampton, SO17 1BJ, UK.
Invert Neurosci. 2018 Nov 7;18(4):14. doi: 10.1007/s10158-018-0219-1.
Caenorhabditis elegans is an informative model to study the neural basis of feeding. A useful paradigm is one in which adult nematodes feed on a bacterial lawn which has been pre-loaded with pharmacological agents and the effect on pharyngeal pumping rate scored. A crucial aspect of this assay is the availability of good quality bacteria to stimulate pumping to maximal levels. A potential confound is the possibility that the pharmacological agent impacts bacterial viability and indirectly influences feeding rate. Here, the actions of nicotine on pharyngeal pumping of C. elegans and on the Escherichia coli bacterial food source were investigated. Nicotine caused an immediate and concentration-dependent inhibition of C. elegans pharyngeal pumping, IC 4 mM (95% CI = 3.4 mM to 4.8 mM). At concentrations between 5 and 25 mM, nicotine also affected the growth and viability of E. coli lawns. To test whether this food depletion by nicotine caused the reduced pumping, we modified the experimental paradigm. We investigated pharyngeal pumping stimulated by 10 mM 5-HT, a food 'mimic', before testing if nicotine still inhibited this behaviour. The IC for nicotine in these assays was 2.9 mM (95% CI = 3.1 mM to 5.1 mM) indicating the depletion of food lawn does not underpin the potency of nicotine at inhibiting feeding. These studies show that the inhibitory effect of nicotine on C. elegans pharyngeal pumping is mediated by a direct effect rather than by its poorly reported bactericidal actions.
秀丽隐杆线虫是研究进食神经基础的一种信息丰富的模型。一种有用的范式是让成年线虫在预先加载了药理剂的细菌菌苔上进食，并对咽部抽吸速率的影响进行评分。该测定的一个关键方面是要有高质量的细菌来将抽吸刺激到最大水平。一个潜在的混杂因素是药理剂可能会影响细菌的活力并间接影响进食速率。在此，研究了尼古丁对秀丽隐杆线虫咽部抽吸以及对大肠杆菌食物来源的作用。尼古丁导致秀丽隐杆线虫咽部抽吸立即出现浓度依赖性抑制，半数抑制浓度（IC）为4 mM（95%置信区间=3.4 mM至4.8 mM）。在5至25 mM的浓度范围内，尼古丁还影响大肠杆菌菌苔的生长和活力。为了测试尼古丁导致的这种食物消耗是否会导致抽吸减少，我们修改了实验范式。在测试尼古丁是否仍抑制这种行为之前，我们研究了由10 mM 5-羟色胺（一种食物“模拟物”）刺激的咽部抽吸。在这些测定中，尼古丁的半数抑制浓度为2.9 mM（95%置信区间=3.1 mM至5.1 mM），表明食物菌苔的消耗并不是尼古丁抑制进食效力的基础。这些研究表明，尼古丁对秀丽隐杆线虫咽部抽吸的抑制作用是由直接作用介导的，而不是由其鲜有报道的杀菌作用介导的。
