Modeling nicotine/THC co-use

项目摘要/摘要 多物质使用(PSU)非常常见，大多数药物使用治疗寻求者报告说 多种物质的使用。此外，PSU在青少年和年轻人中越来越普遍 成年人，这一年龄段高达30%的人报告了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 与其他滥用药物一起使用的最常见的物质是尼古丁。大麻和尼古丁联合- 大麻的使用特别普遍，普通人群中使用大麻的总发生率较高，最高可达 80%的大麻使用者报告说他们也使用尼古丁。最近的流行病学研究表明， 尼古丁与含有THC的产品的联合使用正在增加，特别是在年轻人和同时使用这两种药物的人 同时，与同时食用这两种食物但单独服用的个体相比，总体结果更差 在某些场合。因此，有必要增加我们对尼古丁和THC之间相互作用的了解， 包括它们如何影响彼此的强化特性，在神经功能上是否存在差异 单独对每种物质的反应，以及共同自我管理是否导致倾向增加 对于旧病复发的行为。因此，在这个R21应用程序中，Mary Torregrossa博士和Alan Sve博士的实验室将 在目标1中合作研究尼古丁如何影响自我给药。我们将研究这两个 尼古丁对THC自我给药获得的影响和对已建立的THC摄入量的急性影响。我们会 还要确定尼古丁是否改变了多巴胺的释放和神经活动，以响应核内的THC 伏隔草壳作为研究尼古丁如何改变THC增强效果的第一步。在AIM 2、我们将开发一种双导管系统，允许同时静脉注射THC和THC 尼古丁，另一个目标是将这项技术提供给其他对PSU研究感兴趣的实验室 其他滥用药物。此外，我们将开始确定PSU是否会导致与单核细胞不同的结果。 通过比较线索诱导的复吸中线索激励的、类似复发的药物寻找行为来研究物质的使用 在同时给药THC和尼古丁的大鼠身上进行测试，对比每种物质。在这两个目标中，我们将 比较青春期和成年组的男性和女性，以确定结果是否基于年龄的不同 和/或性爱。特别是，我们感兴趣的是青少年是否特别容易患上 尼古丁/THC组合的强化增强效应可能解释了糖尿病发病率的增加 尼古丁和大麻在年轻人中共同使用。总体而言，项目的成果将为今后的赠款提供基础 可进一步探讨PSU及其治疗的神经机制和长期功能结局的应用 治疗方面的影响。

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.