Gender differences in drug abuse

描述（由申请人提供）：女性开始使用可卡因，比男性更早进入治疗，并且在摄入时比男性更严重地使用可卡因。因此，妇女从最初使用到依赖的发展速度比男子快。这种“伸缩”效应反映了依赖性障碍的医学后果和行为/心理因素特征的发展的较短时间过程。提出的研究是理解吸毒行为的诱导和表达的结构-功能关系以及这种行为在男性和女性中的长期后果的根本重要的第一步。在这个建议中，我们试图确定激素和发育的事件，产生一个性二态性的多巴胺上升系统，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，介导这些性别差异。在大脑的发育过程中，有两次激素会影响大脑的组织。在大鼠中，这些发生在围产期，并再次在围青春期。提出实验来检验这一假设，即增强的脆弱性的女性可卡因滥用是依赖于缺乏暴露于性腺激素在关键的围产期，以及随后暴露于卵巢激素在青春期前后。可卡因自我给药将被用作主要结局指标。人类在青春期获得吸毒行为是成年后药物滥用问题的一个强有力的预测因素。我们假设，在青春期前后的激素暴露的发病有助于增加脆弱性的加强和/或长期后果的可卡因治疗在男性和女性。我们将确定青春期是否是雌性大鼠与雄性大鼠自我施用可卡因的脆弱性增强的时期。或者，也有可能青少年并不更容易受到精神兴奋剂成瘾特性的影响，但在青春期接触这些药物的长期后果导致成年后的易感性增加，这种可能性也将被研究。最后，组织和发展的影响，对可卡因的反应的性别差异的神经基础，将检查从纹状体和核多巴胺透析液。这些实验是探索可卡因滥用脆弱性的性别差异影响纹状体和纹状体核的程度的第一步。妇女比男子更容易对可卡因上瘾。提出的实验将调查神经发育过程，有助于这种性别差异的药物滥用使用临床前模型。该项目的长期目标是，在更好地了解易上瘾的神经基础的基础上，为男子和妇女制定更好的干预和治疗方案。

DESCRIPTION (provided by applicant): 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. Women are more vulnerable to becoming addicted to cocaine than are men. The experiments proposed will investigate the neurodevelopmental processes that contribute to this gender difference in drug abuse using a preclinical model. The long-term goal of this project is to develop better intervention and treatment protocols for both men and women based on an improved understanding of neural basis of vulnerability to addiction.