Neural Mechanisms Underlying Individual Differences in 3,4-Methylenedioxymethamph

描述（由申请人提供）：3，4-亚甲二氧基甲基苯丙胺（MDMA;摇头丸）是一种苯丙胺衍生物，在过去二十年中滥用率不断上升，特别是在青少年和未成年人中。临床数据和动物数据都表明，MDMA的使用模式和滥用该药物的可能性存在很大程度的个体差异。因此，拟议研究的总体目标是（a）进一步表征我们在大鼠中观察到的MDMA相关行为的个体差异，（B）确定预测后续成瘾样行为的特定行为，以及（c）确定这些个体差异的神经基础。为此，我们将首先在我们最近开发的行为致敏范例中运行大鼠，在该范例中，我们操纵药物给药的背景，使得只有大约一半的动物表达对MDMA的行为致敏。随后，我们将确定在复发的动物模型中，对MDMA的行为敏感性的个体差异是否与成瘾样行为有关。最后，为了开始绘制出MDMA寻求行为的复发回路，我们将联合收割机与内侧前额叶皮质的离散子区域的暂时利多卡因失活相结合，内侧前额叶皮质是一个大脑区域，似乎是一个共同的解剖学基底，各种刺激通过该区域聚集以驱动药物寻求行为。拟议的研究结果应该提供独特的洞察力的神经机制的MDMA的行为影响的个体差异。这些类型的临床前研究与成瘾样行为相关的神经行为特征对于开发人类药物滥用和成瘾的改进治疗策略至关重要。 公共卫生相关性：这项研究将有助于我们了解与动物对成瘾行为的脆弱性增加有关的神经和行为特征。因此，这些发现可能有助于开发人类药物滥用和成瘾的改进治疗方案。

DESCRIPTION (provided by applicant): 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is an amphetamine derivative that has seen an increasing abuse rate over the past two decades, particularly in adolescent and young-adult populations. Both clinical and animal data suggest that there is a high degree of individual variability in the pattern of MDMA use and in the drug's potential for abuse. Thus, the overall goals of the proposed research are to (a) further characterize the individual differences in MDMA-related behaviors that we have observed in rats, (b) determine the specific behaviors that are predictive of subsequent addiction-like behaviors, and (c) determine the neural underpinnings of these individual differences. To do this, we will first run rats in our recently developed behavioral sensitization paradigm in which we manipulate the context of drug administration such that only approximately half of the animals express behavioral sensitization to MDMA. Subsequently, we will determine if individual differences in behavioral sensitization to MDMA are related to addiction-like behaviors in an animal model of relapse. Finally, to begin mapping out the circuitry of relapse to MDMA- seeking behavior, we will combine this behavioral testing with temporary lidocaine inactivation of discrete sub-regions of medial prefrontal cortex, a brain region that appears to be a common anatomical substrate through which a variety of stimuli converge to drive drug-seeking behavior. Results of the proposed study should provide unique insight into the neural mechanisms underlying individual differences in the behavioral effects of MDMA. These types of preclinical investigations into the neurobehavioral traits that are related to addiction-like behaviors are crucial to developing improved treatment strategies for human drug abuse and addiction. PUBLIC HEALTH RELEVANCE: This research will contribute to our understanding of the neural and behavioral traits related to animals' increased vulnerability to addiction-like behaviors. Therefore, the findings may aid in the development of improved treatment options for human drug abuse and addiction.