Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, United States.
Drug Alcohol Depend. 2012 Jul 1;124(1-2):63-9. doi: 10.1016/j.drugalcdep.2011.12.011. Epub 2012 Jan 13.
Acquisition of nicotine self-administration in rodents is relatively difficult to establish and measures of acquisition rate are sometimes confounded by manipulations used to facilitate the process. This study examined acquisition of nicotine self-administration without such manipulations and used mathematical modeling to define the criterion for acquisition.
Rats were given 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0-0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined for individual rats by the higher likelihood of reinforcers obtained across sessions fitting a logistic over a constant function according to the corrected Akaike Information Criterion (AICc).
For rats that acquired self-administration, an AICc-based multi-model comparison demonstrated that the asymptote (highest number of reinforcers/session) and mid-point of the acquisition curve (h; the number of sessions necessary to reach half the asymptote) varied by nicotine dose, with both exhibiting a negative relationship (the higher the dose, the lower number of reinforcers and the lower h).
The modeling approach used in this study provides a way of defining acquisition of nicotine self-administration that takes advantage of all data from individual subjects and the procedure used is sensitive to dose differences in the absence of manipulations that influence acquisition (e.g., food restriction, prior food reinforcement, conditioned reinforcers).
在啮齿类动物中获得尼古丁自我给药相对困难,并且获得率的测量有时会因促进该过程的操作而混淆。本研究在没有这些操作的情况下检查了尼古丁自我给药的获得情况,并使用数学模型来定义获得的标准。
大鼠在配备有主动和被动杠杆的室中接受 20 次每日 2 小时的 20 次疗程,每周 6 天。每次主动杠杆按压都会导致尼古丁强化(0-0.06mg/kg,IV),并且两个杠杆都缩回 20 秒以进行超时,而被动杠杆按压则没有后果。根据校正的 Akaike 信息准则(AICc),通过个体大鼠在跨课程中更有可能获得奖励的情况,通过逻辑函数拟合来定义个体大鼠的获得情况。
对于获得自我给药的大鼠,基于 AICc 的多模型比较表明,渐近线(每个疗程获得的最高奖励数)和获得曲线的中点(h;达到渐近线一半所需的疗程数)因尼古丁剂量而异,两者均呈负相关(剂量越高,奖励数越低,h 值越低)。
本研究中使用的建模方法提供了一种定义尼古丁自我给药获得的方法,该方法利用了个体受试者的所有数据,并且该程序在没有影响获得(例如,食物限制、先前的食物强化、条件强化)的操作的情况下,对剂量差异敏感。