Aversion learning in rats and shrews

我的研究项目旨在了解口味和/或情境线索与药物之间的联系的本质。我们评估了恶心、恐惧和药物奖励在刺激反应中与奖励或厌恶药物配对的作用。我们的工作揭示了一个矛盾的发现，即在老鼠身上，一种有益的药物会产生对与其配对的味道的回避，但会产生对与其配对的环境的偏好。虽然奖励药物和产生恶心的药物都能让老鼠回避味道，但只有恶心的药物会在再次接触味道时产生条件厌恶反应。这表明，呕吐药物和奖励药物产生的味觉回避有不同的机制。我们的工作旨在通过评估血清素系统（可能产生恶心）和内源性大麻素系统（可能缓解恶心）对大鼠（对毒素不呕吐）和鼩鼱呕吐的条件厌恶反应的操纵，更好地理解这种分离。由于恶心的神经生物学还没有被很好地理解，由恶心配对的味道或恶心配对的环境引起的条件厌恶反应可以作为研究这一现象的有效啮齿动物模型。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，与老鼠不同，鼩鼱实际上对与有益药物搭配的味道产生了偏好。最后，我们也对上下文线索和药物之间的关联感兴趣，使用条件地板偏好范式。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。我们的项目跨越了心理学、药理学和神经生物学的传统界限，不仅有助于理解学习的基本过程，而且有助于了解这些过程如何影响食物选择、鸦片成瘾和胃肠道不适。我的研究计划在未来5年的具体目标包括评估：1)条件厌恶和条件回避学习的分离，2)大鼠和鼠的新恐惧症、厌恶和回避的比较研究，3)内源性大麻素和血清素对条件厌恶的中枢调节，4)情境诱发条件厌恶反应的调节机制，5)内源性大麻素系统在纳洛酮诱发吗啡戒断的情感特性调控中的作用

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.**