冲动选择作为雄性和雌性大鼠静脉注射可卡因自我给药习得及可卡因觅药行为恢复的预测指标。

Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats.

作者信息

Perry Jennifer L, Nelson Sarah E, Carroll Marilyn E

机构信息

Division of Pharmacology and Toxicology, Minneapolis Medical Research Foundation, Minneapolis, MN 55404, USA.

出版信息

Exp Clin Psychopharmacol. 2008 Apr;16(2):165-77. doi: 10.1037/1064-1297.16.2.165.

Abstract

Drug abuse and impulsive choice are related in humans. In female rats, impulsive choice predicted the rate of acquisition of IV cocaine self-administration. The objectives of the present experiments were to: (a) compare impulsive choice in males and females, (b) extend previous research on impulsive choice and acquisition of cocaine self-administration to males, and (c) compare males and females during maintenance, extinction, and reinstatement of cocaine-seeking behavior. Male and female rats were trained on an adjusting delay task in which a response on one of two levers yielded one food pellet immediately, and a response on the other resulted in three pellets after an adjusting delay that decreased after responses on the immediate lever and increased after responses on the delay lever. A mean adjusted delay (MAD) was used as the quantitative measure of impulsivity. In Experiment 1, MADs were analyzed for sex differences. In Experiment 2, acquisition of cocaine self-administration was examined in rats selected for high (HiI; MADs < or =9 seconds) or low (LoI; MADs > or =13 seconds) impulsivity. In Experiment 3, HiI and LoI groups were compared on maintenance and extinction of cocaine self-administration and cocaine-primed reinstatement of drug-seeking behavior. There were no sex differences in impulsive choice; however, HiI male and female rats acquired cocaine self-administration faster than their LoI counterparts. LoI females responded more on a cocaine-associated lever during maintenance and extinction than HiI females, but HiI females showed greater reinstatement of cocaine-seeking behavior than all other groups at the highest dose tested (15 mg/kg). Thus, individual differences in impulsive choice were associated with differences in cocaine-seeking behavior. Impulsive choice and sex may be additive vulnerability factors in certain phases of drug abuse.

摘要

药物滥用与冲动选择在人类中存在关联。在雌性大鼠中,冲动选择可预测静脉注射可卡因自我给药的习得率。本实验的目的是:(a)比较雄性和雌性的冲动选择;(b)将先前关于冲动选择与可卡因自我给药习得的研究扩展至雄性;(c)比较雄性和雌性在可卡因寻求行为的维持、消退和恢复过程中的表现。雄性和雌性大鼠接受了一项调整延迟任务的训练,在该任务中,对两个杠杆之一的反应会立即产生一粒食物丸,而对另一个杠杆的反应会在调整延迟后产生三粒食物丸,该延迟会在立即杠杆的反应后减少,在延迟杠杆的反应后增加。平均调整延迟(MAD)被用作冲动性的定量指标。在实验1中,分析了MAD的性别差异。在实验2中,对选择了高冲动性(HiI;MADs≤9秒)或低冲动性(LoI;MADs≥13秒)的大鼠进行了可卡因自我给药的习得研究。在实验3中,比较了HiI组和LoI组在可卡因自我给药的维持和消退以及可卡因引发的药物寻求行为恢复方面的表现。冲动选择上不存在性别差异;然而,HiI雄性和雌性大鼠比LoI大鼠更快地习得可卡因自我给药。在维持和消退阶段,LoI雌性大鼠在与可卡因相关的杠杆上的反应比HiI雌性大鼠更多,但在最高测试剂量(15mg/kg)下,HiI雌性大鼠比所有其他组表现出更强的可卡因寻求行为恢复。因此,冲动选择的个体差异与可卡因寻求行为的差异相关。冲动选择和性别可能是药物滥用某些阶段的附加易感性因素。

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