Social support, oxytocin and motivation for methamphetamine

社会支持、催产素和甲基苯丙胺的动机

• 批准号: 10152565
• 负责人: JILL B. BECKER
• 金额: $ 43.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10152565
• 关键词: Abstinence; Acute; Amphetamines; Animal Model; Animals; Attenuated; Behavior; Categories; Chronic; Cocaine; Dependence; Dopamine; Dose; Electrodes; Exposure to; Female; Goals; Housing; Individual; Individual Differences; Intervention; Lead; Loneliness; Measures; Mediating; Methamphetamine; Methamphetamine dependence; Michigan; Motivation; Mus; Nucleus Accumbens; Oxytocin; Periodicity; Pharmaceutical Preparations; Prevention; Property; Public Health; Rattus; Reporting; Research; Rewards; Role; Scanning; Self Administration; Sex Differences; Social Environment; Social support; Stress and Coping; System; Testing; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Universities; Woman; Women' s Role; addiction; attenuation; carbon fiber; craving; effective therapy; experience; experimental study; improved; male; men; methamphetamine effect; methamphetamine exposure; methamphetamine use; neuromechanism; novel; prevent; protective effect; psychologic; response; sex; social; stimulant abuse; traumatic event

Addiction to methamphetamine (METH) is a major public health concern, however there are no effective treatments. Although METH is used by both men and women, women are younger when they start using METH, and show higher rates of dependence compare to men. Women also report a higher exposure to traumatic events and often start using to cope with psychological problems. Social support has a positive influence on stress-coping and might also have protective effects against addiction and help promote decreased motivation to take METH. Females show greater motivation for cocaine than male rats and social housing (pair housing) attenuates the motivation for cocaine in females but not males. Here we investigate whether oxytocin (OT) mediates the effects of social housing on motivation for METH. It is hypothesized that the effects of social housing are mediated by OT-dependent attenuation of dopamine (DA) release in the nucleus accumbens core (NAcC) after drug taking is established and that these effects will be greater in females than in males. Previous research has established that social housing attenuates the METH-induced increase in DA in dialysate from the NAc, and chronic low dose OT attenuates the motivation for METH in female rats. The long- term goal of this project is to understand how social housing influences the rewarding effects of METH in males and females, the role of OT in this regard, and whether chronic intranasal OT may be a therapeutic agent for treatment of psychostimulant abuse in females and/or males. We will also investigate DA responses in the nucleus accumbens fast-scan cyclic voltammetry (FSCV) in isolated and socially-housed male and female rats. The results of these studies will provide an indication of the role of DA in the nucleus accumbens to mediate the effects of social housing and OT on motivation for METH. We will also explore whether chronic intranasal OT can be used as a therapeutic agent for the treatment of METH-addiction.

甲基苯丙胺（METH）成瘾是一个主要的公共卫生问题，但没有有效的 治疗。虽然METH男女都使用，但女性开始使用时更年轻 甲基苯丙胺，并显示出比男子更高的依赖率。女性还报告说， 创伤事件，并经常开始使用，以科普心理问题。社会支持具有积极的 影响压力应对，也可能对成瘾有保护作用，并有助于促进 减少服用冰毒的动机。 雌性大鼠比雄性大鼠表现出更大的可卡因动机和社会住房（对住房）减弱 女性吸食可卡因的动机，而男性没有在这里，我们调查是否催产素（OT）介导的 社会住房对METH动机的影响。据推测，社会住房的影响是 通过OT依赖性衰减多巴胺（DA）的释放介导的丘脑核核心（NAcC）后， 吸毒是确定的，这些影响在女性中比在男性中更大。 先前的研究已经确定，社会住房减弱了在糖尿病患者中由METH诱导的DA增加。 透析液从NAc，和慢性低剂量OT减弱的动机，甲基在雌性大鼠。很长的- 本项目的长期目标是了解社会住房如何影响男性的METH奖励效应 和女性，OT在这方面的作用，以及慢性鼻内OT是否可能是治疗剂， 治疗女性和/或男性的精神兴奋剂滥用。我们还将调查DA反应， 在隔离和社会圈养的雄性和雌性大鼠中，用快速扫描循环伏安法（FSCV）测定了大鼠的丘脑核。 这些研究的结果将提供一个指示的作用，DA在脑桥核介导 社会住房和OT对METH动机的影响。我们还将探讨慢性鼻内 OT可用作治疗剂用于治疗METH成瘾。