Kolokotroni K Z, Rodgers R J, Harrison A A
Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK,
Psychopharmacology (Berl). 2014 Feb;231(3):567-80. doi: 10.1007/s00213-013-3270-y. Epub 2013 Sep 15.
Understanding an individual's vulnerability to drug addiction has important implications for the development of effective personal treatment plans. Although theories acknowledge impulsive behaviour as a key component of drug addiction, little is known about the influence of trait impulsivity on an individual's susceptibility to the effects of psychostimulants on impulsivity at critical phases of the addiction cycle.
This study investigated the short and longer-term effects of chronic nicotine administration on impulsive choice in rats selected for high (HI) and low impulsivity (LI) on a delay discounting task. Rats prepared with subcutaneously osmotic mini-pumps received either nicotine (3.16 mg/kg/day [freebase]) or saline for 7 days. Performance was assessed during chronic treatment, early and late withdrawal, and in response to acute nicotine challenges following prolonged abstinence.
Chronic nicotine increased impulsive choice in LI but not HI animals. Spontaneous withdrawal was associated with a nicotine abstinence syndrome, the early stages of which were characterised by opposing effects on impulsive choice in HI and LI animals. A transient decrease in impulsivity was observed in HI animals whilst the LI group remained more impulsive for up to 1 week following drug termination. Following normalisation of behaviour, acute nicotine challenges (0.125, 0.25, 0.5 mg/kg, SC) markedly increased impulsive choice regardless of trait impulsivity and drug history.
The results indicate that only LI individuals are vulnerable to chronic drug- and withdrawal-induced impairments in self-control which may increase the likelihood of the transition to, and maintenance of, nicotine dependence.
了解个体对药物成瘾的易感性对于制定有效的个人治疗计划具有重要意义。尽管理论上认为冲动行为是药物成瘾的关键组成部分,但关于特质冲动性在成瘾周期关键阶段对个体对精神兴奋剂影响冲动性的易感性的影响知之甚少。
本研究调查了慢性尼古丁给药对在延迟折扣任务中被选择为高冲动性(HI)和低冲动性(LI)的大鼠冲动选择的短期和长期影响。用皮下渗透微型泵制备的大鼠接受尼古丁(3.16毫克/千克/天[游离碱])或生理盐水,持续7天。在慢性治疗期间、早期和晚期戒断期间以及长期禁欲后对急性尼古丁挑战的反应中评估行为表现。
慢性尼古丁增加了LI动物的冲动选择,但对HI动物没有影响。自发戒断与尼古丁戒断综合征有关,其早期阶段的特征是对HI和LI动物的冲动选择有相反的影响。在HI动物中观察到冲动性短暂下降,而LI组在药物终止后长达1周内仍保持更高的冲动性。行为恢复正常后,急性尼古丁挑战(0.125、0.25、0.5毫克/千克,皮下注射)显著增加了冲动选择,无论特质冲动性和药物使用史如何。
结果表明,只有LI个体容易受到慢性药物和戒断引起的自我控制损害,这可能会增加向尼古丁依赖转变和维持的可能性。