Department of Psychiatry, University of Minnesota, MMC 392, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2010 Feb;208(2):211-22. doi: 10.1007/s00213-009-1721-2. Epub 2009 Dec 2.
In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress.
The purpose of this study was to compare adolescent and adult rats on drug-, cue-, and stress-induced reinstatement of cocaine-seeking behavior.
On postnatal days 23 (adolescents) and 90 (adults), rats were implanted with intravenous catheters and trained to lever press for i.v. infusions of cocaine (0.4 mg/kg) during two daily 2-h sessions. The rats then self-administered i.v. cocaine for ten additional sessions. Subsequently, visual and auditory stimuli that signaled drug delivery were unplugged, and rats were allowed to extinguish lever pressing for 20 sessions. Rats were then tested on cocaine-, cue-, and yohimbine (stress)-induced cocaine seeking using a within-subject multicomponent reinstatement procedure.
Results indicated that adolescents had heightened cocaine seeking during maintenance and extinction compared to adults. During reinstatement, adolescents (vs adults) responded more following cocaine- and yohimbine injections, while adults (vs adolescents) showed greater responding following presentations of drug-associated cues.
These results demonstrated that adolescents and adults differed across several measures of drug-seeking behavior, and adolescents may be especially vulnerable to relapse precipitated by drugs and stress.
在人类和动物研究中，青春期标志着对药物初始使用和随后滥用的易感性增加的时期。青少年可能特别容易复发，而药物滥用的一个关键方面是它是一种慢性复发性疾病。然而，对于易感性因素（如青春期）如何与引发复发的条件相关知之甚少，这些条件可能是由药物本身、与药物相关的线索或压力引发的。
本研究的目的是比较青少年和成年大鼠在药物、线索和应激诱导的可卡因寻求行为复吸中的表现。
在出生后第 23 天（青少年）和第 90 天（成年），大鼠被植入静脉导管，并在两个每日 2 小时的时间段内接受静脉内可卡因输注的按压杆训练（0.4mg/kg）。然后，大鼠进行了另外 10 次静脉内可卡因自我给药。随后，断开表示药物输送的视觉和听觉刺激，让大鼠进行 20 次按压杆消退训练。然后，使用多成分复吸程序，对大鼠进行可卡因、线索和育亨宾（应激）诱导的可卡因寻求测试。
结果表明，与成年大鼠相比，青少年在维持和消退期间可卡因寻求行为增加。在复吸期间，与成年大鼠（相比），青少年在可卡因和育亨宾注射后表现出更多的反应，而成年大鼠（相比）在呈现与药物相关的线索后表现出更多的反应。
这些结果表明，青少年和成年大鼠在几种药物寻求行为测量中存在差异，青少年可能特别容易受到药物和压力引发的复发的影响。
