PAVLOVIAN CONDITIONING PROCESSES INVOLVING NICOTINE

涉及刺激-尼古丁关联的条件反射（学习）过程被认为是导致持续滥用烟草制品的一个主要因素。本提案将使用动物模型来阐明环境刺激和尼古丁之间条件关联的获取和表达过程。在这个准备过程中，一个不同的环境反复与尼古丁配对，相对于控制条件，会引起活性的增强。这种增强的活动被认为是环境和尼古丁的运动刺激作用之间存在关联的证据。具体目标1将评估运动活动增强的竞争性解释——兴奋性巴甫洛夫条件反射与抑制性条件反射或新颖性诱导活动。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，条件反射试验的数量，环境和尼古丁之间的时间关系）。在此过程中，将确定更优的调节程序。具体目标3将研究尼古丁预暴露是否会减弱基于传统巴甫洛夫条件反射范式的理论预测的随后的尼古丁运动条件反射，或者尼古丁预暴露是否会促进药物条件反射领域的条件反射效应。该目的还将确定尼古丁的条件和非条件运动效应如何随不同的暴露前方案（例如，环境、数量、剂量间隔、连续或间歇给药）而变化。阐明巴甫洛夫药物条件反射的习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.