Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin

灵长类动物的支配行为和社会地位影响着生理、神经结构、行为和反应 滥用药物。催产素（OXT）是一种与支配行为相关的肽激素，可调节可卡因 自我给药并与海马（HC）体积相关。男性统治通常依赖于 而女性的统治通常依赖于梳理。我们假设不同的行为 与男性和女性的社会结构有关的因素解释了可卡因自我给药的性别差异 在群居食蟹猴中观察到。因此，支配行为和性别都是适度的药物， 然而，关于这两个变量相互作用的研究却严重缺失。我们假设 优势行为是一个重要的因素，占生物相关的变异性研究与非- 人类灵长类动物因此，我们提出了一个前瞻性研究的影响，性别，月经周期，优势， 行为和可卡因自我给药对恒河猴OXT水平和HC体积的影响以及 在可卡因自我给药时操纵OXT我们将使用标准化的同性配对互动测试， 获得每只猴子的优势指数。我们的初步数据显示，即使在 单独圈养的非人类灵长类动物，与纹状体多巴胺的释放，可卡因的强化作用， 安非他明的食欲和HC的量因此，优势指数是一个相关的措施， 与社会和非社会行为者有关的行为特征。目标1.决定支配地位的影响- 雄性（n = 10）和雌性（n = 10）恒河猴HC体积和OXT水平的指数。目标2a。确定 自我管理的静脉注射可卡因和可口的食物作为优势指数的函数的强化作用。 目标2b。确定月经周期和优势指数对自我强化效应的影响， 静脉注射可卡因和可口的食物目标3：确定（9个月）可卡因自身的影响， 施用对HC体积和OXT水平的影响作为优势指数的函数。目标4。确定 a）通过急性施用SOC 1增加OXT水平的作用，由Iain MacGregor开发，B） 通过急性施用OXT拮抗剂2，5-二酮哌嗪（DTP）降低OXT效应，和c） SOC1 + DTP对可卡因自我给药的影响作为优势指数的函数。 冲击我们将动态和前瞻性地跟踪雄性和雌性恒河猴的HC体积和OXT水平 为了评估这些措施在多大程度上是吸毒的风险因素， 吸毒，或者两者兼而有之。通过使用自然变化的优势指数，我们将能够梳理出 环境因素造成的。这一建议将提供一个经验基础， 开发催产素系统的生物信息操纵，以及行为信息操纵。 根据男性和女性的社会行为进行治疗。

Dominance behaviors and social status in primates affects physiology, neural structure, behavior and response to drugs of abuse. Oxytocin (OXT), a peptide hormone associated with dominance behavior modulates cocaine self-administration and is associated with hippocampal (HC) volume. Male dominance commonly relies on aggression while female dominance commonly relies on grooming. We hypothesize that the different behaviors associated with male and female social structure account for the sex differences in cocaine self-administration observed in socially-housed cynomolgus monkeys. Thus, both dominance behavior and sex moderate drug response, yet studies on the interaction of these two variables are sorely missing. We hypothesize that dominance behavior is a significant factor accounting for biologically relevant variability in research with non- human primates. Therefore, we propose a prospective study on the effects of sex, menstrual cycle, dominance behavior and cocaine self-administration on OXT levels and HC volume in rhesus monkeys and the effects of manipulating OXT on cocaine self-administration. We will use standardized, same-sex dyad-interaction tests to obtain a dominance-index for each monkey. Our preliminary data show that the dominance-index, even in singly-housed non-human primates, is related to striatal dopamine release, the reinforcing effects of cocaine, the appetitive effects of amphetamine, and HC volume. Thus the dominance-index is a relevant measure of a behavioral trait related to both social and non-social reinforcers. Aim 1. Determine the effect of dominance- index on HC volume and OXT levels in male (n = 10) and female (n = 10) rhesus monkeys. Aim 2a. Determine the reinforcing effects of self-administered i.v. cocaine and palatable food as a function of dominance-index. Aim 2b. Determine the effects of menstrual cycle and dominance-index on the reinforcing effects of self- administered i.v. cocaine and palatable food. Aim 3. Determine the effects of (9 mo) cocaine self- administration on HC volume and OXT levels as a function of the dominance-index. Aim 4. Determine the effects of a) increasing OXT levels by acute administration of SOC1, developed by Iain MacGregor, b) decreasing OXT effects by acute administration of the OXT antagonist 2,5- diketopiperazine (DTP) and c) SOC1 + DTP on cocaine self-administration as a function of the dominance-index. Impact. We will dynamically and prospectively track HC volume and OXT levels in male and female rhesus monkeys in order to assess the extent to which these measures are risk factors for drug use, consequences of drug use, or both. By using naturally varying dominance-indexes, we will be able to tease out the effects of environmental conditions from cocaine taking. This proposal will provide an empirical basis for the development of biologically-informed manipulations of the oxytocin system, and behaviorally-informed treatments based on social behavior for both males and females.