Adolescence, Impulsivity, and Drug Abuse: Sex/Hormones

该项目的总体目标是使用创新的动物模型来研究个体差异， 已成为药物滥用的关键脆弱因素（冲动、青春期、性、荷尔蒙状态， 对非药物奖励的贪婪）。要解决的主要问题是，冲动，一个定义 青少年的特点，与更容易受到药物滥用的影响有关， 青春期（与成年期），以及冲动是否与性腺激素的增加有关， 发生在这个关键的发展阶段。冲动的行为模型;例如，延迟折扣 （选择一个小的即时奖励与一个大的延迟奖励），和去/不去任务（抑制行为期间， 将使用信号通知的非奖励与奖励时段）。其他行为将与 冲动性测试，以确定它们是否与冲动行为协变，并具有预测价值; 如，寻求药物行为（复发）的消退和恢复（Ext/Reinst）。最后，冲动 测量将与药物的新奇寻求行为的各种指数相关（例如，可卡因、海洛因）和 非药物（例如，轮跑和蔗糖摄入）奖励。以下是对应的具体目标 通过4个拟议的实验：1）为了解决冲动是一个主要因素的程度 青少年与成年人相比更容易滥用药物。雄性和雌性青春期和成年大鼠将 组内和组间比较冲动性、延迟折扣（DD）和Go/No的两个指标， 去任务的食物或静脉注射可卡因。2)为了研究冲动的青少年是否会 冲动的成年人使用DD和Go/No-go程序来获得可卡因和食物奖励。低（Lol）和高 (Hil)还将比较冲动男性和女性组的可卡因寻求行为的Ext/Reinst。第三章 为了确定是否是循环性腺激素或先天发育/ 青少年冲动和/或药物滥用的性别差异的组织差异 和成年人使用DD或Go/No-go程序，将比较5组：a）卵巢切除的女性 (OVX)B）OVX+雌激素替代（OVX + E），c）去势雄性（CAST），d）假手术雌性 （假手术）和e）假手术雄性。4)研究冲动性与协变因素之间的关系 在预测药物滥用方面的冲动性。选择大鼠进行Hil和Lol（DD和Go/No-go）检测 以及其他奖励所维持的行为。其他组别将被选为 药物（可卡因、海洛因）和非药物（跑轮子、蔗糖）强化高和低强迫行为 奖励和测试的冲动性措施的冲动性和贪婪的双向比较， 药物或非药物奖励。对觅药行为中冲动性的研究将增加我们的理解 病因学、预防和治疗药物滥用。

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.