Social support, oxytocin and motivation for methamphetamine

摘要/摘要 对甲基苯丙胺(冰毒)上瘾是一个主要的公共卫生问题，然而没有有效的 治疗。虽然男性和女性都使用冰毒，但女性开始使用冰毒时更年轻 冰毒，并表现出比男性更高的依赖率。女性也报告有更高的暴露在 创伤事件，并经常开始使用，以应对心理问题。社会支持有积极的作用 对应对压力有影响，也可能对戒瘾有保护作用，有助于促进 吸食冰毒的动机减弱。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(配对住房)会减弱女性的可卡因动机，但不会削弱男性的动机。在这里，我们调查 催产素(OT)是否介导了社会住房对冰毒动机的影响。据推测， 社会住房的影响是通过OT依赖的多巴胺(DA)释放的减弱而介导的。 在吸毒后，伏隔核核心(NAC)被确定，并且这些影响将在女性中更大 而不是男性。先前的研究已经证实，社会住房可以缓解冰毒诱导的 NAC透析液中的DA和慢性低剂量OT可减弱雌性大鼠的冰毒动机。 实验将检验以下假设：1)有了社会住房，动物的意志就越占优势 与非优势配对和单独饲养的动物相比，DA的释放较低。2) 慢性鼻腔催产素治疗将调节DA对冰毒的反应；3)性别差异和/或 DA释放的个体差异将预测冰毒自我给药的动机。社交 安慰剂减轻冰毒诱导的雌性大鼠NAC和OT透析液中DA的增加 减弱雌性大鼠服用冰毒的动力。将使用快速扫描循环伏安法来研究 社会住房和慢性鼻腔催产素对NAC DA释放的影响以确定是否有性行为 冰毒诱导的DA释放的差异以及个体差异是否可以预测冰毒的动机 在随后的自我管理研究中。

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.