Mathieu-Kia A M, Kellogg S H, Butelman E R, Kreek M J
Rockefeller University, Laboratory on the Biology of Addictive Diseases, Box 171, 1230 York Avenue, New York, NY 10021-6399, USA.
Psychopharmacology (Berl). 2002 Jul;162(2):102-18. doi: 10.1007/s00213-002-1096-0. Epub 2002 May 15.
Recent preclinical behavioral and neurobiological research has characterized important behavioral features and has identified neurobiological substrates that may underlie nicotine reinforcement and addiction.
To examine recent advances on nicotine exposure in preclinical models, from three perspectives: (a) the chronopharmacokinetics of nicotine, (b) behavioral studies on nicotine reinforcement, withdrawal, and reinstatement/relapse, and (c) effects of nicotine on neurobiological substrates after repeated exposure.
Preclinical studies can be used to operationally model selected aspects of nicotine reinforcement, withdrawal, and reinstatement or relapse. These may be used to investigate the functional in vivo consequences of acute and long-term changes in neuronal acetylcholine receptor populations that follow nicotine exposure. Behavioral studies focusing on distinct stages of nicotine exposure (e.g., active reinforcement vs. cessation or reinstatement) may also be used in parallel with studies on dopaminergic function, a proposed substrate for the reinforcing effects of nicotine, and of opioid receptor function, a possible site of neuroadaptations secondary to nicotine exposure.
While no single current animal model may capture the experience of human smoking or nicotine addiction, increasingly, separate animal models are capturing the full spectrum of behavioral and neurobiological dimensions of this complex condition.
近期临床前行为学和神经生物学研究已明确了重要的行为特征,并确定了可能构成尼古丁强化作用和成瘾基础的神经生物学底物。
从三个方面探讨临床前模型中尼古丁暴露的最新进展:(a)尼古丁的时辰药代动力学,(b)尼古丁强化、戒断及复吸/复发的行为学研究,(c)反复暴露后尼古丁对神经生物学底物的影响。
临床前研究可用于对尼古丁强化、戒断及复吸或复发的选定方面进行操作性建模。这些研究可用于探究尼古丁暴露后神经元乙酰胆碱受体群体急性和长期变化的体内功能后果。聚焦于尼古丁暴露不同阶段(如主动强化与戒断或复吸)的行为学研究,也可与关于多巴胺能功能(尼古丁强化作用的假定底物)及阿片受体功能(尼古丁暴露继发神经适应性改变的可能位点)的研究并行开展。
虽然目前没有单一的动物模型能够完全模拟人类吸烟或尼古丁成瘾的体验,但越来越多的单独动物模型正在涵盖这种复杂情况的行为和神经生物学各个方面。