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: 10355816
• 负责人: JILL B. BECKER
• 金额: $ 6.53万
• 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/10355816
• 关键词: Amphetamines; Animal Model; Animals; Attenuated; Behavior; Budgets; Chronic; Cocaine; Data; Dependence; Dopamine; Dose; Electrodes; Exposure to; Female; Goals; Housing; Individual; Individual Differences; Lead; Loneliness; Measures; Mediating; Methamphetamine; Methamphetamine dependence; Michigan; Motivation; Mus; Nucleus Accumbens; Oxytocin; Partner in relationship; Pattern; Periodicity; Pharmaceutical Preparations; Pilot Projects; Prevention; Property; Public Health; Rattus; Reporting; Research; Rewards; Role; Scanning; Self Administration; Sex Differences; Social Dominance; Social Environment; Social support; Stress and Coping; Testing; Therapeutic Agents; Universities; Woman; Women' s Role; addiction; attenuation; carbon fiber; effective therapy; experience; experimental study; improved; male; men; methamphetamine effect; methamphetamine exposure; methamphetamine use; neuromechanism; novel; parent grant; prevent; protective effect; psychologic; response; sex; social; stimulant abuse; traumatic event; trend

Summary/Abstract 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 (NAc) 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 females rats. Experiments will test the following hypotheses: 1) with social housing the more dominant animal will have lower DA release compared to the non-dominant pair and individually housed animals. 2) Chronic intranasal OT treatment will modulate the DA response to METH; and 3) sex differences and/or individual differences in DA release will predict the motivation for self-administration of METH. Social housing attenuates the METH-induced increase in DA in dialysate from the NAc of female rats and OT attenuates motivation for METH in female rats. Fast scan cyclic voltammetry will be used to investigate the effect of social housing and chronic intranasal OT on DA release in NAc to determine if there are sex differences and whether individual differences in METH-induced DA release predict motivation for METH during subsequent self-administration studies.

总结/摘要 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， 同居（成对同居）减弱了女性吸食可卡因的动机，但对男性没有影响。在这里我们调查 催产素（OT）是否介导了社会住房对METH动机的影响。它是假设 社会住房的影响是通过OT依赖的多巴胺（DA）释放衰减介导的， 在服用药物后，建立了一个神经核核心（NAc），这些影响在女性中更大 比男性多。以前的研究已经确定，社会住房削弱了甲基苯丙胺引起的增加， NAc透析液中的DA和慢性低剂量OT减弱了雌性大鼠对METH的动机。 实验将检验以下假设：1）在社会住房中， 具有较低的DA释放相比，非优势对和单独圈养的动物。（二） 慢性鼻内OT治疗将调节DA对METH的反应;和3）性别差异和/或 DA释放的个体差异将预测METH自我给药的动机。社会 圈养减弱了MET诱导的雌性大鼠NAc和OT透析液中DA的增加 减弱雌性大鼠对甲基苯丙胺的动机。快速扫描循环伏安法将用于研究 社会住房和慢性鼻内OT对NAc中DA释放影响以确定是否存在性别 差异以及METH诱导的DA释放的个体差异是否可预测METH的动机 在随后的自我给药研究中。