Modeling nicotine/THC co-use

项目概要/摘要 多物质使用（PSU）是非常普遍的，大多数物质使用治疗寻求者报告 使用多种物质。此外，PSU在青少年和年轻人中变得越来越普遍。 成年人，在这个年龄组中，高达30%的人报告PSU。不仅PSU的患病率很高， 但PSU的后果也被认为比使用单一物质的个人更糟糕。一 与任何其他滥用药物一起使用的最常见物质是尼古丁。尼古丁和尼古丁- 使用尤其普遍，一般人群中大麻使用的总体发生率较高， 80%的大麻使用者报告他们也使用尼古丁。最近的流行病学研究表明， 尼古丁与含THC产品的共同使用正在增加，特别是在年轻人中，以及那些同时使用这两种药物的人 与此同时，他们的总体结果比那些同时消费两者但单独消费的人更差。 场合因此，有必要增加我们对尼古丁和THC之间相互作用的理解， 包括它们如何影响彼此的强化特性，是否有神经系统的差异， 相对于每种物质单独给药的反应，以及联合自我给药是否导致倾向性增加 因为他有类似复发的行为因此，在这个R21应用中，玛丽·托雷格罗萨博士和艾伦·斯维德博士的实验室将 合作研究目标1，尼古丁如何影响THC自我管理。我们将研究 尼古丁对获得THC自我给药的影响以及对已确定的THC摄入量的急性影响。我们将 还可以确定尼古丁是否会改变多巴胺的释放和神经活动，以响应细胞核中的THC 这是研究尼古丁如何改变THC增强作用的第一步。在Aim中 2，我们将开发一种双导管系统，允许同时静脉自我管理的四氢大麻酚， 尼古丁，额外的目标是使该技术可用于对PSU研究感兴趣的其他实验室， 其他滥用药物。此外，我们将开始确定PSU是否会导致与单药治疗不同的结果， 通过比较线索诱导复吸中线索驱动、复发样药物寻求行为来评估药物使用 在大鼠中进行测试，这些大鼠自我给予THC和尼古丁，而不是单独给予每种物质。在这两个目标中，我们将 比较青少年和成年男性和女性群体，以确定结果是否因年龄而异 和/或性特别是，我们感兴趣的是青少年是否特别容易受到 尼古丁/THC组合的增强效果可能解释了 尼古丁和大麻在年轻人中的共同使用。总的来说，该项目的成果将为未来的赠款提供基础 应用，可以进一步探讨神经机制和长期的功能结果PSU及其 治疗影响。

Project Summary/Abstract Polysubstance use (PSU) is extremely common, with the majority of substance use treatment seekers reporting the use of multiple substances. Moreover, PSU is becoming increasingly common among adolescents and young adults, with up to 30% of individuals in this age group reporting PSU. Not only is the prevalence of PSU high, but the consequences of PSU are also thought to be worse than for individuals who use single substances. One of the most common substances to be used with any other drug of abuse is nicotine. Marijuana and nicotine co- use is particularly common, with higher overall incidence of marijuana use in the general population and up to 80% of marijuana users reporting that they also use nicotine. Recent epidemiological studies indicate that the co-use of nicotine with THC containing products is increasing, particularly in youth, and those that use both drugs at the same time have worse overall outcomes than those individuals that consume both, but on separate occasions. Thus, there is a need to increase our understanding of the interactions between nicotine and THC, including how they affect the reinforcing properties of each other, whether there are differences in neural responses relative to each substance alone, and whether co-self-administration leads to increased propensity for relapse-like behavior. Thus, in this R21 application, the labs of Drs. Mary Torregrossa and Alan Sved will collaborate to investigate in Aim 1, how nicotine influences THC self-administration. We will examine both the effect of nicotine on acquisition of THC self-administration and acute effects on established THC intake. We will also determine if nicotine alters dopamine release and neural activity in response to THC in the nucleus accumbens shell as a first step toward investigating how nicotine may alter the reinforcing effects of THC. In Aim 2, we will develop a dual catheter system to allow simultaneous intravenous self-administration of THC and nicotine, with the additional goal of making the technique available to other labs interested in PSU research of other drugs of abuse. In addition, we will begin to determine if PSU leads to different outcomes relative to mono- substance use by comparing cue-motivated, relapse-like drug seeking behavior in a cue-induced reinstatement test in rats that self-administered both THC and nicotine versus each substance alone. In both aims, we will compare adolescent and adult groups of males and females to determine if outcomes are different based on age and/or sex. In particular, we are interested in whether or not adolescents are particularly susceptible to the reinforcement-enhancing effects of nicotine/THC combinations that might explain the increased incidence of nicotine and cannabis co-use in youth. Overall, the outcomes of the project will provide the basis for future grant applications that can further probe the neural mechanisms and long-term functional outcomes of PSU and its treatment implications.