Social Influences on drug reward and monoamines

描述（由申请人提供）：项目名称-药物奖励和单胺的社会影响：青少年社会剥夺，社会线索和性别差异。早年生活中的逆境，包括青春期发生的不良事件，可能会导致对药物成瘾的脆弱性，或者相反，对药物成瘾的抵抗力。可能影响这些事件是否产生成瘾的脆弱性或抵抗力的因素包括与个人有关的因素，如性别;所涉及的药物类别，如阿片类药物或精神兴奋剂;以及吸毒发生的背景。在包括大鼠在内的社会性物种中，青少年社会剥夺（隔离养育）已被用作青少年逆境的模型，其产生社会行为的变化以及对药物滥用反应的改变。隔离养育可以减少滥用药物的奖励特性，从而导致对成瘾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的背景的重要组成部分。社会互动可以是非常有益的，特别是在青春期，社会线索可以加强药物的奖励作用。隔离养育可以增加社会互动的重要性，从而导致成瘾的社会背景维度的脆弱性。因此，隔离养育可能通过影响药物暴露的两个不同维度产生对药物成瘾的脆弱性和抵抗力。在这里，它是预测的影响，社会背景上的奖励效果的药物将取决于社会历史（社会剥夺或社会经验）的个人在关键时期的青春期。此外，在隔离饲养和药物暴露的反应中存在性别差异，并且这些影响在男性和女性之间可能不同。拟议的研究通过提出以下问题来解决这些问题：暴露于阿片类羟考酮或精神兴奋剂可卡因期间的社会线索是否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产生更大的影响？这些效应的机制是否与涉及奖赏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解决。具体目的1是使用条件性位置偏爱来确定隔离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。具体目标2是确定在药物暴露期间的社会线索的影响，细胞外多巴胺和5-羟色胺在核延髓和内侧前额叶皮质的隔离或组饲养的雄性和雌性大鼠使用体内微透析。了解药物和社会奖励如何相互作用，以及如何通过先前的社会经验和个体的性别来介导，可以有助于制定针对高危个体的干预措施。 公共卫生相关性：该建议探讨了社会剥夺在青春期的作用，社会线索的奖励属性和滥用药物的神经化学改变属性的影响，并询问这是否取决于受试者的性别。这些结果有可能提供证据表明，早期逆境可以与吸毒环境相互作用，影响成瘾的脆弱性，并可能有助于制定针对高危人群的干预措施。

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.