Aversion learning in rats and shrews

老鼠和鼩鼱的厌恶学习

• 批准号: RGPIN-2016-03629
• 负责人: Parker, Linda
• 金额: $ 4.44万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631479
• 关键词: Aversion; learning; rats; shrews

My program of research is aimed at understanding the nature of associations that develop between tastes and/or contextual cues and drugs. We evaluate the role of nausea, fear and drug reward in motivating responding to stimuli following pairing with rewarding or aversive drugs. Our work has shed light on the paradoxical finding that in rats a rewarding drug produces avoidance of a taste with which it is paired, but a preference for a context with which it is paired. Although rewarding drugs and drugs that produce nausea both produce taste avoidance in rats, only nauseating drugs produce a conditioned disgust reaction during re-exposure to the taste. This suggests that different mechanisms are involved in taste avoidance produced by emetic drugs and rewarding drugs. Our work is aimed at better understanding this dissociation by evaluating manipulations of the serotonin system (which may produce nausea) and the endocannabinoid system (which may relieve nausea) on conditioned disgust reactions in rats (which do not vomit in response to toxins) and vomiting in shrews. Since the neurobiology of nausea is not well understood, conditioned disgust reactions elicited by a nausea-paired flavor or a nausea-paired context may serve as an effective rodent model to investigate this phenomenon. This work has also led to investigations of evolutionary mechanisms that may guide food selection in rats and shrews; for instance, unlike rats, shrews actually develop a preference for a taste paired with a rewarding drug. Finally, we are also interested in associations that occur between contextual cues and drugs, using a conditioned floor preference paradigm. Our work is aimed at understanding the early phases of opiate dependence, relapse following extinction training and the role of the endocannabinoid system in the extinction of such learning. Our program cuts across the traditional boundaries of psychology, pharmacology and neurobiology, contributing not only to understanding basic processes of learning, but also how those processes impact on food selection, opiate addiction and gastrointestinal malaise. The specific objectives of my research program over the next 5 years include the evaluation of the: 1) Dissociation between conditioned disgust and conditioned avoidance learning, 2) Comparative studies of neophobia, disgust and avoidance in rats and S. murinus, 3) Central regulation of conditioned disgust by endocannabinoids and serotonin, 4) Mechanisms governing the regulation of contextually elicited conditioned disgust reactions, 5) Role of the endocannabinoid system in regulation of the affective properties of naloxone-precipitated morphine withdrawal.

我的研究计划旨在了解口味和/或上下文线索和药物之间发展的关联的性质。我们评估的作用，恶心，恐惧和药物奖励的激励响应刺激配对奖励或厌恶药物。我们的工作揭示了一个自相矛盾的发现，即在大鼠中，奖励性药物会产生对与之配对的味道的回避，但会产生对与之配对的环境的偏好。虽然奖励药物和产生恶心的药物都能使大鼠产生味觉回避，但只有消除恶心的药物在再次接触味觉时会产生条件性恶心反应。提示催吐剂和奖赏剂产生味觉回避的机制不同。我们的工作旨在更好地理解这种分离，通过评估操纵的血清素系统（可能会产生恶心）和内源性大麻素系统（可能会缓解恶心）的条件性厌恶反应大鼠（不呕吐的毒素）和呕吐的鼩。由于恶心的神经生物学还没有得到很好的理解，条件性恶心反应引起的恶心配对的味道或恶心配对的背景下，可以作为一个有效的啮齿动物模型来研究这种现象。这项工作还导致了对可能指导大鼠和鼩 鼱食物选择的进化机制的研究;例如，与大鼠不同，鼩 鼱实际上对与奖励药物配对的味道产生了偏好。最后，我们也感兴趣的关联，上下文线索和药物之间发生的，使用条件地板偏好范例。我们的工作旨在了解阿片类药物依赖的早期阶段，消退训练后的复发以及内源性大麻素系统在这种学习消退中的作用。我们的计划跨越了心理学，药理学和神经生物学的传统界限，不仅有助于了解学习的基本过程，而且还有助于了解这些过程如何影响食物选择，阿片类药物成瘾和胃肠道不适。本研究计划在未来5年内的具体目标包括：1）条件性厌恶和条件性回避学习的分离; 2）大鼠和S. murinus，3）内源性大麻素和5-羟色胺对条件性厌恶的中枢调节，4）调节情境引发的条件性厌恶反应的机制，5）内源性大麻素系统在调节纳洛酮诱发的吗啡戒断的情感特性中的作用。