Social support and addiction: cross talk between oxytocin and dopamine

社会支持和成瘾：催产素和多巴胺之间的对话

• 批准号: 8383255
• 负责人: JILL B. BECKER
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8383255
• 关键词: Acute; Affect; Age; American; Animal Housing; Animals; Anti-Anxiety Agents; Attenuated; Behavior Therapy; Chronic; Cocaine; Cocaine Abuse; Cocaine Dependence; Data; Dependence; Disease; Dopamine; Dose; Drug Addiction; Drug usage; Effectiveness; Exhibits; Female; Gender; Goals; Housing; Infusion procedures; Intake; Laboratory Rat; Lead; Life; Loneliness; Mediating; Mental Health; Microdialysis; Motivation; Naltrexone; Neurophysiology - biologic function; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Peptides; Pharmaceutical Preparations; Property; Rattus; Reinforcement Schedule; Relapse; Research; Rewards; Risk; Risk Factors; Role; Self Administration; Self-Administered; Sex Characteristics; Signal Transduction; Social Behavior; Social Environment; Social Impacts; Social support; Societies; Stress; Substance Use Disorder; Testing; Therapeutic Agents; Treatment outcome; Woman; Work; addiction; behavior influence; cocaine exposure; cocaine use; craving; drug of abuse; effective therapy; emotional distress; experience; human female; improved; in vivo; insight; male; men; pre-clinical research; protective effect; receptor; recreational drug use; research study; response; social; stressor

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.

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，其中39.5%是女性。妇女开始使用可卡因和接受治疗的年龄比男子早，在接受治疗时使用可卡因的程度比男子更严重。事实上，从最初使用到依赖，雌性人类和大鼠的发展速度比雄性更快，并且有更大的动机获得可卡因。目前对所有物质使用障碍的治疗（我们缺乏对可卡因使用障碍的任何药物治疗）并不能减轻压力增强的药物使用。我们有一个非常有限的了解性别差异，在应对压力及其对药物自我管理的影响，特别是在药物和治疗结果的影响。虽然压力会增加吸毒和复吸，但积极的社会环境可能有助于减少吸毒。后者可以通过减少压力水平，从而减少药物摄入量来发挥作用。初步数据显示，在实验室大鼠中，成对的住房减少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）是一个很可能的候选人弥合差距之间的差距成瘾和社会环境的保护作用。我们假设OT与社会住房相结合，将减少服用可卡因的动机。我们将调查是否外源OT可以减少动机，以采取可卡因，如果这是受社会住房条件，重点是女性。此外，我们假设OT和成对住房通过调节可卡因诱导的多巴胺释放来发挥作用。因此，我们将研究是否对住房和OT，或两者的组合，影响可卡因诱导的多巴胺释放在脑桥核，比较可卡因的幼稚和自我管理经验丰富的大鼠。这些研究的结果将提供一个指标，如果OT可以作为治疗剂用于治疗可卡因成瘾，如果社会接触的存在将增加OT的效果。 公共卫生相关性：可卡因成瘾的有效治疗是有限的，似乎是男性比女性更成功。尽管更多的男子对可卡因上瘾，但妇女使用毒品的情况也在增加，而且滥用毒品对妇女的上瘾影响更大。这项研究对心理健康很重要，因为它将调查 社会因素对女性滥用药物的影响，以及这如何影响神经功能。深入了解社会支持的保护特性，最终可能会改善女性和男性可卡因成瘾的治疗选择。