Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin

吸食可卡因的前因和后果：催产素的影响

• 批准号: 10408141
• 负责人: Suzette M Evans
• 金额: $ 62.02万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10408141
• 关键词: Accounting; Acute; Affect; Aggressive behavior; Amphetamines; Animals; Behavior; Behavioral; Cocaine; Corpus striatum structure; Data; Data Set; Desire for food; Development; Dopamine; Drug usage; Estrogens; Female; Food; Grooming; Hippocampus (Brain); Intake; Intravenous; Luteal Phase; Macaca fascicularis; Macaca mulatta; Measures; Mediating; Menstrual cycle; Monkeys; Oxytocin; Palate; Peripheral; Pharmaceutical Preparations; Physiology; Primates; Progesterone; Prospective Studies; Rattus; Research; Risk Factors; Running; Same-sex; Self Administration; Sex Differences; Social Behavior; Social status; Standardization; Structure; System; Testing; antagonist; base; behavioral response; cocaine self-administration; cohort; diketopiperazine; drug of abuse; indexing; male; neurogenesis; nonhuman primate; peptide hormone; proliferative phase Menstrual cycle; prospective; reinforcer; relating to nervous system; response; sex; social; social attachment; social structure; standard measure; trait

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.

灵长类动物的主导行为和社会地位影响生理，神经结构，行为和反应 滥用药物。催产素（OXT），一种与优势行为相关的肽激素调节可卡因 自我管理，与海马（HC）体积有关。男性主导地位通常依赖 侵略而女性优势通常依赖于修饰。我们假设不同的行为 与男性和女性社会结构相关的可卡因自我管理性别差异 在社会上的cynomolgus猴子中观察到。因此，优势行为和性中等药物 响应，但是对这两个变量的相互作用的研究却记到了。我们假设这一点 优势行为是对生物学相关的研究的重要因素，在非 - 人类灵长类动物。因此，我们提出了一项有关性别，月经周期和优势影响的前瞻性研究 行为和可卡因在恒河猴中的oxt水平和HC体积上的自我管理以及 在可卡因自我管理上操纵牛。我们将使用标准化的同性二元相互作用测试 为每只猴子获得一个优势指数。我们的初步数据表明，即使在 单人体非人类灵长类动物，与纹状体多巴胺释放有关，可卡因的增强作用， 苯丙胺和HC体积的食欲。因此，主导地位是对 行为特征与社会和非社会增强剂有关。目标1。确定优势的影响 - 男性（n = 10）和女性（n = 10）恒河猴的HC体积和OXT水平的指数。目标2a。决定 自我管理的i.v.的增强作用可卡因和可口的食物与优势指数的关系。 目标2B。确定月经周期和优势索引对自我增强作用的影响 静脉内管理可卡因和可口的食物。目标3。确定（9个月）可卡因自我的影响 HC体积和OXT水平的给药是主导地位的函数。目标4。确定 a）急性给药SOC1的效果，由Iain MacGregor开发，b） 通过急性给药2,5-二甲苯吡嗪（DTP）和C）急性施用oxt效应。 SOC1 + DTP关于可卡因自我给药是统治地位的函数。 影响。我们将动态和前瞻性地跟踪男性和女恒河的HC量和OXT水平 猴子以评估这些措施是吸毒的风险因素的程度 吸毒，或两者兼而有之。通过使用自然变化的主导地位，我们将能够逗弄 可卡因服用的环境条件。该建议将为 开发催产素系统的生物知识操纵和行为知名度 基于男性和女性的社会行为的治疗。