Social support and addiction: cross talk between oxytocin and dopamine

描述(由申请人提供)：可卡因滥用在过去十年中有所增加，目前有240万美国人使用可卡因，在上瘾的人中，39.5%是女性。女性开始使用可卡因和接受治疗的年龄比男性更早，而且在治疗摄入时使用可卡因的情况比男性更严重。事实上，从最初的使用到依赖，女性人类和大鼠的进展速度比男性更快，获得可卡因的动机也更大。目前对所有物质使用障碍的治疗(我们缺乏任何针对可卡因使用障碍的药物治疗)并不能缓解压力增强的药物使用。我们对应激源反应的性别差异及其对药物自我给药的影响的了解非常有限，特别是在药物治疗的背景下和对治疗结果的影响。虽然压力会增加药物摄入和复发，但积极的社会环境可能有助于减少药物使用。后者可以通过降低压力水平来发挥作用，从而减少药物摄入量。初步数据显示，实验大鼠的配对住所降低了雌性大鼠服用可卡因的动机，但对雄性大鼠没有影响。催产素(OT)可能是一种弥合成瘾和社会环境保护作用之间的桥梁的候选药物。我们假设，加班与社会住房相结合，将降低吸食可卡因的动机。我们将调查外源性OT是否会降低吸食可卡因的动机，以及这是否受到社会住房条件的影响，重点是女性。此外，我们假设OT和配对住房通过调节可卡因诱导的多巴胺释放来发挥它们的作用。因此，我们将研究配对安置和催产素，或两者的组合，是否影响可卡因诱导的伏隔核多巴胺释放，比较可卡因幼稚和自我给药经验的大鼠。这些研究的结果将提供一个迹象，表明OT是否可以用作治疗可卡因成瘾的药物，以及社会接触的存在是否会增强OT的效果。 公共卫生相关性：可卡因成瘾的有效治疗方法有限，男性似乎比女性更有效。尽管越来越多的男性对可卡因上瘾，但女性的毒品使用量正在增加，滥用毒品对女性的上瘾影响更大。这项研究对心理健康很重要，因为它将调查 社会因素对滥用药物对女性的影响，以及这如何影响神经功能。对社会支持的保护性特性的洞察最终可能导致改善男女可卡因成瘾的治疗选择。

DESCRIPTION (provided by applicant): Cocaine abuse has increased during the last decade so that 2.4 million Americans currently use cocaine, and of those addicted 39.5 percent are female. Women begin using cocaine and enter treatment at earlier ages than men and have more severe cocaine use at treatment intake than men. In fact, from initial use to dependence female humans and rats progress at a faster rate than males and have greater motivation to obtain cocaine. Current treatments for all substance use disorders (and we lack any medication treatment for cocaine use disorders) do not mitigate stress-potentiated drug use. We have a very limited understanding of sex differences in response to stressors and their effect on drug self-administration, particularly in the context of medication and implications for treatment outcome. While stress augments drug intake and relapse, a positive social environment may serve to reduce drug use. The latter could act by reducing stress levels, and thereby decreasing drug intake. Preliminary data show that pair housing in laboratory rats reduced the motivation to take cocaine in females, but not in males. Oxytocin (OT) is a likely Candidate for bridging the gap between addiction and the protective effects of a social environment. We hypothesize that OT, in combination with social housing, will reduce the motivation to take cocaine. We will investigate whether exogenous OT can reduce the motivation to take cocaine and if this is influenced by the social housing conditions, focusing on females. Furthermore, we hypothesize that OT and pair housing exert their effects by modulating cocaine- induced dopamine release. Therefore, we will investigate if pair- housing and OT, or the combination of both, affect cocaine-induced dopamine release in the nucleus accumbens, comparing cocaine-naive and self-administration-experienced rats. The results from these studies will provide an indication if OT can be used as a therapeutic agent for the treatment of cocaine- addiction, and if the presence of social contacts will augment the effects of OT. PUBLIC HEALTH RELEVANCE: Effective treatments for cocaine addiction are limited, and appear to be more successful in men than women. Even though more men are addicted to cocaine, drug use in women is increasing, and the addictive effects of drugs of abuse are greater in women. This research is important for mental health as it will investigate the impact of social factors on the effects of drugs of abuse in females, and how this affects neural function. Insight into the protective properties of social support could ultimately lead to improved treatment options for cocaine addiction in both women and men.