Adolescence, Impulsivity, and Drug Abuse: Sex/Hormones

这个项目的总体目标是使用创新的动物模型来研究个体差异， 已成为药物滥用的主要易受伤害因素(冲动、青春期、性、荷尔蒙状况和 对非药物奖励的渴望)。要解决的主要问题是，冲动，一种定义 青春期的特征与药物滥用的易感性有关，这在 青春期(与成年期相比)，以及冲动是否与性腺激素的增加有关 发生在发展的这一关键阶段。冲动的行为模型；例如，延迟折扣 (选择小的-立即的奖励与大延迟的奖励)，以及进行/不进行任务(行为持续抑制) 有信号的非奖励与奖励期间)将被使用。其他行为将与 冲动性测试，以确定它们是否与冲动行为相同，并具有预测价值； AS、吸毒行为的灭绝和恢复(Ext/Reinst)(复发)。最后，冲动 措施将涉及毒品(如可卡因、海洛因)的各种寻奇行为指数和 非药物奖励(例如，跑轮和摄入蔗糖)。以下是对应的具体目标 通过4个拟议的实验：1)解决冲动在多大程度上是一个主要因素 青少年与成年人相比，更容易受到药物滥用的影响。雄性和雌性青春期和成年鼠将 比较组内和组间的两种冲动性指标，延迟折扣(DD)和Go/No- 去做食物或静脉注射任务。可卡因。2)调查冲动的青少年是否会成为 冲动的成年人使用DD和去/不去程序来获得可卡因和食物奖励。低(LOL)和高 (HIL)冲动的男性和女性也将在寻找可卡因行为的Ext/Reinst上进行比较。3) 以确定它是循环性腺激素的增加还是先天发育/ 青少年冲动和/或药物滥用的性别差异的组织差异 与使用DD或Go/No-Go程序的成年人进行比较，5组将被比较：a)去卵巢的女性 (OVX)，b)OVX加雌激素替代(OVX+E)，c)去势雄性(CAST)，d)假手术雌性 (假)和(E)假雄性。4)考察冲动与相关因素之间的关系 在预测药物滥用时的冲动。将选择大鼠进行HIL和LOL(DD和Go/No-Go)并进行测试 在其他方面，以及通过其他奖励维持的行为。其他组将被选为 毒品(可卡因、海洛因)和非毒品(跑轮、蔗糖)强化行为的高低 在冲动和贪婪的双向比较中，在冲动的测量上进行奖励和测试 毒品或非毒品奖励。研究寻毒行为中的冲动现象将加深我们对毒品行为的认识 药物滥用的病因、预防和治疗。

The overall objective of this project is to use innovative animal models to study individual differences that have emerged as key vulnerability factors in drug abuse (impulsivity, adolescence, sex, hormonal status, and avidity for nondrug rewards). The main question to be addressed is whether impulsivity, a defining characteristic of adolescence, is related to the enhanced vulnerability to drug abuse that is seen more in adolescence (vs. adulthood), and whether impulsivity is related to the increase in gonadal hormones that occurs during this critical phase of development. Behavioral models of impulsivity; such as, delay discounting (choosing a small-immediate vs. a large-delayed reward), and the Go/No-go task (inhibition of behavior durinc signaled nonreward vs. reward periods) will be used. Other behaviors will be compared to the results of the impulsivity tests to determine whether they covary with impulsive behavior and have predictive value; such as, extinction and reinstatement (Ext/Reinst) of drug-seeking behavior (relapse). Finally, impulsivity measures will be related to various indices of novelty-seeking behavior for drug (e.g., cocaine, heroin) and nondrug (e.g., wheel-running, and sucrose intake) rewards. The following are specific aims that correspond with the 4 proposed experiments: 1) To address the extent to which impulsivity is a major factor contributing to vulnerability to drug abuse in adolescents vs. adults. Male and female adolescent and adult rats will be compared within and between groups on two measures of impulsivity, delay-discounting (DD) and the Go/No- go tasks for food or i.v. cocaine. 2) To investigate the question of whether impulsive adolescents become impulsive adults using the DD and Go/No-go procedures for cocaine and food rewards. Low (Lol) and high (Hil) impulsive male and female groups will also be compared on Ext/Reinst of cocaine-seeking behavior. 3) To determine whether it is an increase in circulating gonadal hormones or innate developmental/ organizational differences that account for the sex differences in impulsivity and/or drug abuse in adolescents and adults using the DD or Go/No-go procedure, 5 groups will be compared: a) ovariectomized females (OVX), b) OVX with estrogen replacement (OVX + E), c) castrated males (CAST), d) sham-operated females (SHAM) and e) SHAM males. 4) To examine the relationship between impulsivity and factors that covary with impulsivity in predicting drug abuse. Rats will be selected for Hil and Lol (DD and Go/No-go) and tested on the other measure as well as for behavior maintained by other rewards. Other groups will be selected as high and low for behaviors reinforced by drug (cocaine, heroin) and nondrug (wheel-running,sucrose) rewards and tested on measures of impulsivity for a bidirectional comparison of impulsivity and avidity for drugs or nondrug rewards. The study of impulsivity in drug-seeking behavior will increase our understanding of the etiology, prevention, and treatment of drug abuse.