A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.
A differential role for neuropeptides in acute and chronic adaptive responses to alcohol: behavioural and genetic analysis in Caenorhabditis elegans.
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DOI：
10.1371/journal.pone.0010422
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发表时间：
2010-05-03
期刊：
影响因子：
3.7
通讯作者：
O'Connor V
中科院分区：
文献类型：
--
作者：
Mitchell P;Mould R;Dillon J;Glautier S;Andrianakis I;James C;Pugh A;Holden-Dye L;O'Connor V
人类长期饮酒然后戒酒会引发戒断综合症，包括焦虑、激动，严重时还会出现癫痫发作。低剂量的酒精可以缓解戒断症状，这是一种导致酒精依赖的负强化。这种“戒断缓解”现象提供了乙醇诱导的适应的证据，这种适应重置了神经回路中的信号平衡。我们以此为标准来区分线虫中直接和间接乙醇诱导的适应性行为反应，目的是研究乙醇诱导的神经可塑性的遗传基础。该范例采用“食物竞赛测定”，测试急性和长期接受乙醇处理的动物的感觉运动性能。我们描述了一种多方面的线虫“戒断综合症”。一个特征是，低剂量的乙醇并不能缓解逆转频率的降低，并且很可能是由于抑制进食和缺乏食物的行为状态而导致对乙醇的间接适应。然而，另一方面，由自发的深部身体弯曲组成的异常行为，确实表现出戒断缓解，因此我们认为这是乙醇诱导的可塑性的表现。钾通道 slo-1 是秀丽隐杆线虫中的候选乙醇效应子，对于此处描述的反应不是必需的。然而，神经肽缺陷的突变体egl-3对戒断具有抵抗力（尽管它仍然表现出对乙醇的急性反应）。这种对神经肽的依赖性不涉及 NPY 样受体 npr-1，该受体先前与秀丽隐杆线虫乙醇戒断有关。因此，其他神经肽途径介导这种效应。这些数据与哺乳动物研究产生共鸣，这些研究报告了许多神经肽参与酒精的慢性反应，包括促肾上腺皮质激素释放因子（CRF）、阿片类药物、速激肽以及 NPY。这表明神经肽在乙醇诱导的可塑性中具有进化上保守的作用，并为酒精对简单模型系统的影响进行遗传分析开辟了道路。
Prolonged alcohol consumption in humans followed by abstinence precipitates a withdrawal syndrome consisting of anxiety, agitation and in severe cases, seizures. Withdrawal is relieved by a low dose of alcohol, a negative reinforcement that contributes to alcohol dependency. This phenomenon of ‘withdrawal relief’ provides evidence of an ethanol-induced adaptation which resets the balance of signalling in neural circuits. We have used this as a criterion to distinguish between direct and indirect ethanol-induced adaptive behavioural responses in C. elegans with the goal of investigating the genetic basis of ethanol-induced neural plasticity. The paradigm employs a ‘food race assay’ which tests sensorimotor performance of animals acutely and chronically treated with ethanol. We describe a multifaceted C. elegans ‘withdrawal syndrome’. One feature, decrease reversal frequency is not relieved by a low dose of ethanol and most likely results from an indirect adaptation to ethanol caused by inhibition of feeding and a food-deprived behavioural state. However another aspect, an aberrant behaviour consisting of spontaneous deep body bends, did show withdrawal relief and therefore we suggest this is the expression of ethanol-induced plasticity. The potassium channel, slo-1, which is a candidate ethanol effector in C. elegans, is not required for the responses described here. However a mutant deficient in neuropeptides, egl-3, is resistant to withdrawal (although it still exhibits acute responses to ethanol). This dependence on neuropeptides does not involve the NPY-like receptor npr-1, previously implicated in C. elegans ethanol withdrawal. Therefore other neuropeptide pathways mediate this effect. These data resonate with mammalian studies which report involvement of a number of neuropeptides in chronic responses to alcohol including corticotrophin-releasing-factor (CRF), opioids, tachykinins as well as NPY. This suggests an evolutionarily conserved role for neuropeptides in ethanol-induced plasticity and opens the way for a genetic analysis of the effects of alcohol on a simple model system.
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DOI：
10.1111/j.1530-0277.2008.00639.x
发表时间：
2008-05-01
影响因子：
3.2
作者：
Davis, Justin R.;Li, Yuri;Rankin, Catharine H.
通讯作者：
Rankin, Catharine H.
影响因子：
5.3
作者：
Gehlert, Donald R.;Cippitelli, Andrea;Heilig, Markus
通讯作者：
Heilig, Markus
DOI：
10.1097/01.alc.0000141817.15993.98
发表时间：
2004-10-01
影响因子：
3.2
作者：
Berger, KH;Heberlein, U;Moore, MS
通讯作者：
Moore, MS
DOI：
10.1073/pnas.0409009101
发表时间：
2005-03-01
影响因子：
11.1
作者：
Gray, JM;Hill, JJ;Bargmann, CI
通讯作者：
Bargmann, CI
DOI：
10.1111/j.1530-0277.2006.00087.x
发表时间：
2006-05-01
影响因子：
3.2
作者：
Cowmeadow, RB;Krishnan, HR;Atkinson, NS
通讯作者：
Atkinson, NS