Harris Andrew C, Pentel Paul R, Lesage Mark G
Minneapolis Medical Research Foundation, 914 South 8th St. S-3 Labs, 860, Minneapolis, MN 55404, USA.
Psychopharmacology (Berl). 2007 Oct;194(3):395-402. doi: 10.1007/s00213-007-0848-2. Epub 2007 Jul 5.
Animals trained to self-administer a variety of addictive drugs exhibit a temporary increase in response rate when saline is substituted for the drug (i.e., an "extinction burst"). However, the presence of an extinction burst in animal models of nicotine self-administration (NSA) has not been studied extensively.
The objective of the study was to examine the prevalence, magnitude, and correlates of an extinction burst in nicotine-seeking behavior using data from a previously published study and recently trained animals.
Rats were trained to self-administer nicotine (0.03 mg/kg per infusion) during daily 23-h sessions. Saline extinction was subsequently arranged, followed by reacquisition of NSA for some animals.
There was no increase in the daily infusion rate on the first day of extinction. However, a significant increase (35%) in mean peak 2-h infusion rates was observed within the first extinction session, indicative of an extinction burst. Greater extinction burst magnitude was correlated with higher infusion rates during the first 2 h of baseline sessions and smaller decreases in infusion rate at the end of extinction. In addition, animals with the slowest initial rates of extinction exhibited the fastest rates of reacquisition when unlimited access to nicotine was restored.
A modest increase in drug-seeking behavior occurred early within the first extinction session in rats trained to self-administer nicotine in unlimited access sessions. The presence of an extinction burst in nicotine-seeking behavior suggests similar mechanisms underlying extinction of NSA and self-administration of other drugs of abuse in animals and also parallels a similar phenomenon sometimes observed in smokers.
经训练能自行摄入多种成瘾性药物的动物,在以生理盐水替代药物时(即“消退爆发”),反应率会出现短暂升高。然而,尼古丁自行给药(NSA)动物模型中消退爆发的存在尚未得到广泛研究。
本研究的目的是利用先前发表的研究数据以及最近训练的动物,来检验尼古丁寻求行为中消退爆发的发生率、程度及其相关因素。
大鼠在每日23小时的实验时段内接受训练,自行摄入尼古丁(每次输注0.03毫克/千克)。随后安排生理盐水消退实验,部分动物之后重新进行尼古丁自行给药实验。
消退第一天的每日输注率没有增加。然而,在第一次消退实验期间,观察到平均2小时峰值输注率显著增加(35%),表明出现了消退爆发。更大的消退爆发程度与基线实验最初2小时内较高的输注率以及消退结束时输注率较小的下降相关。此外,最初消退速度最慢的动物在恢复无限制获取尼古丁时,重新获取药物的速度最快。
在无限制获取实验中经训练自行摄入尼古丁的大鼠,在第一次消退实验早期,药物寻求行为出现适度增加。尼古丁寻求行为中消退爆发的存在表明,在动物中,尼古丁自行给药和其他滥用药物自行给药的消退背后存在相似机制,并且与吸烟者中有时观察到的类似现象相似。