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Gender differences in drug abuse

药物滥用的性别差异

基本信息

批准号：
8448220
负责人：
JILL B. BECKER
金额：
$ 27.16万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-09-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8448220
关键词：
Acute Addictive Behavior Adolescence Adolescent Adult Age Androgens Beer Behavior Behavioral Brain Characteristics Cocaine Cocaine Abuse Corpus striatum structure Dependence Development Disease Dopamine Drug abuse Estradiol Event Exposure to Female Goals Gonadal Hormones Growth Habits Hormonal Hormones Human Hypothalamic structure Intake Intervention Mediating Medical Nucleus Accumbens Outcome Measure Ovarian hormone Perinatal Pharmaceutical Preparations Pre-Clinical Model Predisposition Preoptic Areas Process Property Psychological Factors Rattus Research Rodent Self Administration Self-Administered Sex Characteristics Staging Structure Testing Time Treatment Protocols Woman addiction base cocaine exposure cocaine use dopamine system improved male men neurotransmission peripubertal period primary outcome relating to nervous system research study response sex

项目摘要

Women begin using cocaine, enter treatment at earlier ages than men, and have more severe cocaine use at intake than men. Thus, women progress from initial use to dependence faster than men do. This "telescoping" effect reflects a briefer time course for the development of medical consequences and behavioral/psychological factors characteristic of a dependence disorder. The studies proposed are a fundamentally important first step towards understanding structure-function relations in the induction and expression of drug-taking behavior and the long-term consequences of this behavior in both males and females. In this proposal we seek to identify the hormonal and developmental events that produce a sexually dimorphic ascending dopamine system that results in sex differences in drug abuse liability, and to identify some of the associated neural processes that mediate these sex differences. There are two times during development of the brain when hormones can influence its organization. In the rat these occur during the peri-natal period and again during the peri-pubertal period. Experiments are proposed to test the hypothesis that the enhanced vulnerability of females for cocaine abuse is dependent on the lack of exposure to gonadal hormones during the critical perinatal period, as well as subsequent exposure to ovarian hormones during the peripubertal period. Self-administration of cocaine will be used as the primary outcome measure. Acquisition of drug taking behavior during adolescence in humans is a strong predictor of drug abuse problems as an adult. We hypothesize that onset of hormone exposure during the peri-pubertal period contributes to increased vulnerability for the reinforcing and/or long-term consequences of cocaine treatment in both males and females. We will determine whether adolescence is a period of enhanced vulnerability for female vs. male rats to self-administer cocaine. Alternatively, it is possible that adolescents aren't more vulnerable to the addictive properties of the psychomotor stimulants, but that the long-term consequences of exposure to these drugs during adolescence result in increased susceptibility as an adult, this possibility will be examined as well. Finally, the neural basis of the organizational and developmental influences on sex differences in the response to cocaine will be examined by looking at dopamine in dialysate from striatum and nucleus accumbens. These experiments are a first step towards exploring the extent that sex differences in vulnerability for cocaine abuse impacts the striatum and nucleus accumbens.

女性开始使用可卡因，进入治疗的年龄比男性早，并且使用可卡因的程度更严重比男性多。因此，妇女从最初使用到依赖的发展速度比男子快。这 “伸缩”效应反映了医疗后果发展的较短时间进程，以依赖性障碍为特征的行为/心理因素。拟议的研究是这是理解归纳过程中结构-功能关系的重要的第一步，吸毒行为的表现和这种行为在男性和女性中的长期后果女性在这项建议中，我们试图确定产生性行为的激素和发育事件。二态性多巴胺上升系统，导致药物滥用倾向的性别差异，并确定一些相关的神经过程来调节这些性别差异。在大脑的发育过程中，有两次激素会影响大脑的组织。在这些发生在围产期，并再次发生在围青春期。实验建议测试的假设，增强脆弱性的女性可卡因滥用是依赖于在关键的围产期缺乏性激素的暴露，以及随后的暴露对卵巢激素的影响可卡因的自我管理将被用作主要的结果测量。人类在青春期获得药物服用行为是药物滥用的一个强有力的预测因素成年人的问题。我们假设在青春期前后开始接触激素有助于增加对可卡因治疗的强化和/或长期后果的脆弱性，无论是男性还是女性。我们将确定青春期是否是一个增强脆弱性的时期，雌鼠和雄鼠自我注射可卡因。或者，也有可能青少年易受精神兴奋剂成瘾特性的影响，但长期的后果是，在青春期接触这些药物会导致成年后易感性增加，这种可能性将是也进行了检查。最后，探讨了组织和发展对性别差异影响的神经基础。将通过观察纹状体和核的透析液中的多巴胺来检查对可卡因的反应伏隔核。这些实验是探索性别差异的程度的第一步。易受可卡因滥用影响的纹状体和脑桥核。