Social Influences on drug reward and monoamines

项目名称：社会对毒品奖励和单胺的影响：青少年社会剥夺、社会线索和性别差异。生命早期的逆境，包括发生在青春期的不良事件，可以产生对吸毒成瘾的脆弱性，或者相反，对吸毒成瘾的抵抗力。可能影响这些事件是否产生对成瘾的脆弱性或抵抗力的因素包括与个人有关的因素，例如性别；所涉及的药物类别，如阿片类药物或精神兴奋剂；以及吸毒发生的环境。在包括老鼠在内的群居物种中，青少年社会剥夺（隔离饲养）已被用作青少年逆境的模型，这种逆境会产生社会行为的变化以及对滥用药物的反应的变化。孤立抚养可以减少滥用药物的奖励特性，从而引起对成瘾的内在强化维度的抵抗。越来越多的人认识到，药物暴露期间的社会线索是药物暴露发生环境的重要组成部分。社会互动可能是非常有益的，尤其是在青少年时期，而社会暗示可以增强药物的有益作用。孤立抚养可以增加社会互动的重要性，从而导致成瘾的社会环境维度的脆弱性。因此，隔离抚养可能通过对药物暴露的两个不同维度的影响产生对药物成瘾的脆弱性和抗性。本文预测社会环境对药物奖励效应的影响将取决于个体在青春期关键时期的社会历史（社会剥夺或社会经验）。此外，已知对隔离饲养和药物暴露的反应存在性别差异，这些影响可能在男性和女性之间有所不同。提出的研究通过提出以下问题来解决这些问题：暴露于阿片类药物羟考酮或精神兴奋剂可卡因时的社会线索对青春期被剥夺社会权利的雄性和雌性大鼠的药物寻求行为有更大的影响吗？这些效应的机制是否与奖赏相关的神经回路的神经化学变化有关？这些问题将在两个具体目标中加以解决。具体目的1是利用条件位置偏好确定孤立或群体饲养对社会线索诱导的雄性和雌性大鼠药物寻求行为变化的影响。具体目的2是通过体内微透析确定药物暴露期间社会线索对隔离或群体饲养的雄性和雌性大鼠伏隔核和内侧前额叶皮层细胞外多巴胺和血清素的影响。了解药物和社会奖励是如何相互作用的，以及这种相互作用是如何被先前的社会经验和个体的性别所调节的，可以有助于开发针对高危个体的干预措施。

DESCRIPTION (provided by applicant): Project Title - Social Influences on drug reward and monoamines: Adolescent social deprivation, social clues, and sex differences. Early life adversity, including adverse events that occur during adolescence, can produce vulnerability to, or conversely, resistance to drug addiction. Factors that may influence whether these events produce vulnerability or resistance to addiction include those related to the individual, such as its gender; the drug class involved, such as opioids or psychostimulants; and the context in which drug taking occurs. In social species including rats, adolescent social deprivation (isolation rearing) has been used as a model of adolescent adversity that produces changes in social behavior as well as alterations in the responses to drugs of abuse. Isolation rearing can produce a reduction in the rewarding properties of drugs of abuse, thus causing resistance to the intrinsic reinforcement dimension of addiction. Increasingly, social cues during drug exposure are recognized as an important component of the context in which drug exposure takes place. Social interactions can be highly rewarding, especially during adolescence, and social cues can potentiate the rewarding effects of drugs. Isolation rearing can produce an increase in the importance of social interactions, thus causing vulnerability to the social context dimension of addiction. Thus, isolation rearing may produce both vulnerability and resistance to drug addiction via effects on two different dimensions of drug exposure. Here it is predicted that the influence of social context on the rewarding effects of drugs will depend on the social history (social deprivation or social experience) of the individual during the critical period of adolescence. Moreover, sex differences in the responses to both isolation rearing and drug exposure are known to occur so and these effects may differ between males and females. The proposed research addresses these issues by asking the following questions: Do social cues during exposure to the opioid oxycodone or the psychostimulant cocaine have a greater impact on drug seeking behavior in male and female rats that have been socially deprived during adolescence? Is the mechanism of these effects related to changes in the neurochemistry of neural circuits involved in reward? These questions will be addressed in two specific aims. Specific Aim 1 is to determine the effects of isolation or group rearing on social cue-induced changes in drug- seeking behavior in male and female rats using conditioned place preference. Specific Aim 2 is to determine the effects of social cues during drug exposure on extracellular dopamine and serotonin in the nucleus accumbens and medial prefrontal cortex of isolation- or group-reared male and female rats using in vivo microdialysis. Understanding how drug and social rewards interact and how this may be mediated by the prior social experience and the sex of the individual can contribute to the development of interventions specific to at- risk individuals. PUBLIC HEALTH RELEVANCE: This proposal explores the role of social deprivation during adolescence on the impact of social cues on the rewarding properties and neurochemistry-altering properties of drugs of abuse, and asks whether this depends on the sex of the subject. The results have the potential to provide evidence that early adversity can interact with the drug-taking environment to influence the vulnerability to addiction, and may contribute to the development of interventions specific to at-risk individuals.