Aversion learning in rats and shrews

我的研究项目旨在了解口味和/或背景线索与毒品之间发展起来的联系的本质。我们评估恶心、恐惧和药物奖励在与奖励或厌恶药物配对后对刺激反应的激发作用。我们的工作揭示了一个矛盾的发现，即在老鼠身上，一种有价值的药物会产生对与之配对的味道的回避，但会对与其配对的背景产生偏好。虽然奖励药物和引起恶心的药物都会使大鼠回避味道，但只有恶心的药物在再次接触这种味道时会产生条件性的厌恶反应。这表明，呕吐药物和奖励药物产生的味觉回避涉及不同的机制。我们的工作旨在通过评估5-羟色胺系统(可能会产生恶心)和内源性大麻系统(可能会缓解恶心)对大鼠的条件性厌恶反应(对毒素不会呕吐)和对地鼠的呕吐的操纵，来更好地了解这种解离。由于恶心的神经生物学还不是很清楚，由恶心的味道或恶心的环境引起的条件性厌恶反应可以作为一个有效的啮齿动物模型来研究这一现象。这项工作还导致了对可能指导大鼠和地鼠食物选择的进化机制的研究；例如，与大鼠不同，地鼠实际上会对与有回报的药物配对的味道产生偏好。最后，我们还对上下文线索和药物之间的关联感兴趣，使用条件性场上偏好范式。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亡中的作用。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，不仅有助于了解学习的基本过程，而且还有助于了解这些过程对食物选择、阿片成瘾和胃肠道不适的影响。在接下来的5年里，我的研究计划的具体目标包括评估：1)条件性厌恶和条件性回避学习之间的分离，2)大鼠和S.Murinus中新的恐惧症、厌恶和回避的比较研究，3)内源性大麻素和5-羟色胺对条件性厌恶的中央调节，4)上下文诱发的条件性厌恶反应的调节机制，5)内源性大麻素系统在纳洛酮催促的吗啡戒断的情感特性调节中的作用。

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.