PAVLOVIAN CONDITIONING PROCESSES INVOLVING NICOTINE

涉及刺激-尼古丁关联的条件反射（学习）过程被认为是导致烟草制品持续滥用的一个主要因素。 本建议将使用动物模型来阐明环境刺激和尼古丁之间的条件关联的获得和表达所涉及的过程。 在该制剂中，与尼古丁重复配对的独特环境引起相对于对照条件的活性增强。 这种增强的活性被认为是环境与尼古丁的运动刺激作用之间存在关联的证据。 具体目标1将评估竞争帐户的增强自发活动-兴奋性巴甫洛夫条件反射与抑制性条件反射或新奇诱导的活动。 具体目标2的目标将是操纵在其他巴甫洛夫条件反射准备中发现的程序变量来改变学习（例如，条件反射试验次数、环境与尼古丁之间的时间关系）。 在这样做的过程中，将确定更优化的调节程序。 具体目标3将研究尼古丁预暴露是否会减弱随后的尼古丁运动条件反射，如基于传统巴甫洛夫条件反射范式研究的理论所预测的那样，或者尼古丁预暴露是否会促进条件反射运动效应，如药物条件反射领域的一小部分文献所描述的那样。 这一目标还将确定尼古丁的条件和非条件运动效应如何作为不同暴露前方案的函数而变化（例如，背景、数量、剂量间隔、连续与间歇给药）。 阐明巴甫洛夫药物条件反射的获得和表达的行为过程将对预防和干预策略具有重要意义。

Conditioning (learning) processes involving stimulus-nicotine associations are believed to be a major factor contributing to the continued abuse of tobacco products. The present proposal will use an animal model to elucidate the processes involved in the acquisition and expression of a conditioned association between environmental stimuli and nicotine. In this preparation, a distinct environment that has been repeatedly paired with nicotine comes to elicit an enhancement of activity relative to control conditions. This enhanced activity is taken as evidence for an association between the environment and the locomotor stimulant effects of nicotine. Specific Aim 1 will assess competing accounts of the enhanced locomotor activity --- excitatory Pavlovian conditioning vs. inhibitory conditioning or novelty-induced activity. The goal of Specific Aim 2 will be to manipulate procedural variables found in other Pavlovian conditioning preparations to alter learning (e.g., number of conditioning trials, temporal relation between environment and nicotine). In doing so, more optimal conditioning procedures will be identified. Specific Aim 3 will investigate whether nicotine pre-exposure attenuates subsequent nicotine locomotor conditioning as predicted by theories based on research with traditional Pavlovian conditioning paradigms or whether nicotine pre-exposure facilitates the conditioned locomotor effects as characterized by a smaller set of literature in the drug conditioning field. This aim will also determine how the conditioned and unconditioned locomotor effects of nicotine vary as a function of different pre-exposure protocols (e.g., context, number, interdose interval, continuous vs. intermittent delivery). Elucidating the behavioral processes underlying acquisition and expression of Pavlovian drug conditioning will have important implications for prevention and intervention strategies.