Antecedents and Consequences of Cocaine Taking: Impact of Oxytocin

灵长类动物的优势行为和社会地位影响生理、神经结构、行为和反应 向滥用毒品致敬。催产素(OXT)，一种与优势行为相关的多肽激素，调节可卡因 自我给药，并与海马区(HC)体积有关。男性主导地位通常依赖于 攻击性，而女性的主导地位通常依赖于修饰。我们假设不同的行为 与男性和女性的社会结构相关解释了可卡因自我管理的性别差异 在群居食蟹猴身上观察到的。因此，支配行为和性行为都是适度的药物 然而，关于这两个变量相互作用的研究严重缺乏。我们假设 显性行为是解释与生物相关的变异性的一个重要因素 人类灵长类动物。因此，我们建议对性别、月经周期、优势地位的影响进行前瞻性研究。 行为、可卡因自身给药对恒河猴OXT水平和HC容量的影响 在可卡因自我管理上操纵奥克托。我们将使用标准化的同性二元互动测试来 获取每只猴子的优势指数。我们的初步数据显示，优势指数，即使在 独居非人类灵长类动物，与纹状体多巴胺释放，可卡因的增强作用， 安非他明的食欲作用，以及HC量。因此，优势指数是一种相关的衡量标准 与社会性和非社会性增强者相关的行为特征。目标1.确定显性的影响- 雄性恒河猴(n=10)和雌性恒河猴(n=10)的HC体积和OXT水平指数。目标2a。测定 自我静脉注射的强化作用。可卡因和可口食物作为优势指数的函数。 目标2b。测定月经周期和优势指数对自我调节作用的影响 静脉注射。可卡因和美味的食物。目的3.测定(9mo)可卡因自身的影响 作为优势指数函数的HC容量和OXT水平的给药。目标4.确定 A)由Iain MacGregor开发的急性给药SOC1提高OXT水平的影响，b) 急性给予OXT拮抗剂2，5-二酮基哌嗪(DTP)和c)可降低OXT效应 SOC1DTP对可卡因自我给药作为优势指数函数的影响。 冲击力。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毒品使用的风险因素， 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 吸食可卡因所造成的环境条件。这项建议将为 催产素系统的生物知情操作和行为知情操作的发展 针对男性和女性的基于社会行为的治疗。

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.