Effects of Nicotine on Environmental Stimuli

描述（由申请人提供）：越来越多的证据表明，非尼古丁因素，如与吸烟有关的感官刺激，可能有助于吸烟的维持和复发。在动物模型中，在尼古丁传递过程中仅仅存在视觉刺激就会增加自我给药。尼古丁对非尼古丁刺激反应的几种解释是尼古丁：1)增强由条件强化维持的反应，2)增强由各种环境后果（如食物，光线）维持的反应，3)增加现有反应的激活。不幸的是，自我给药过程混淆了产生尼古丁的反应和产生条件强化物的反应。本研究将解开上述解释，同时将尼古丁的直接影响与条件强化物维持的反应分离开来，使用观察反应程序。这个程序将使我们能够比较尼古丁对老鼠的几种反应的影响（例如，导致食物，光线，灭绝），并建立了控制，以确定已经存在的活动的普遍增加。尼古丁也被证明可以在食物被移除后增强对食物的抵抗力。我们将评估这一发现对条件强化维持的反应的可靠性和普遍性。下面的方案由2个实验组成。实验一将研究几种剂量的尼古丁对不同后果（如初级强化物和条件强化物）维持的反应以及这种反应在消失期间的抗性。实验二将试图区分这些作用是由中枢还是外周机制介导的，通过使用拮抗剂甲胺和六甲溴铵阻断尼古丁。该项目将比较尼古丁对非尼古丁刺激反应影响的不同假设，并将进一步验证一个动物模型，以了解尼古丁对各种环境后果的影响。

DESCRIPTION (provided by applicant): There is growing evidence that non-nicotine factors, such as sensory stimuli associated with smoking, may contribute to the maintenance and relapse of smoking. In animal models, the mere presence of a visual stimulus during nicotine delivery increases self-administration. Several interpretations of the effects of nicotine on responding for non-nicotine stimuli are that nicotine: 1) enhances responding maintained by conditioned reinforcers, 2) enhances responding maintained by various environmental consequences (e.g. food, lights), and 3) causes increased activation of existing responses. Unfortunately, self-administration procedures confound responses that produce nicotine with responses that produce conditioned reinforcers. The present study will disentangle the interpretations listed above, while separating the direct effects of nicotine from responses maintained by conditioned reinforcers, using the observing response procedure. This procedure will allow us to compare effects of nicotine on several responses in rats (e.g. resulting in food, lights, extinction) and has built in controls for identifying general increases in already existing activity. Nicotine has also been shown to enhance resistance of responding maintained by food when food is removed. We will assess the reliability and generality of this finding to responses maintained by conditioned reinforcers. The following proposal consists of 2 experiments. Experiment I will investigate several doses of nicotine on responding maintained by different consequences (e.g., primary and conditioned reinforcers) and resistance of such responding during extinction. Experiment II will seek to distinguish whether these effects are mediated by central or perhipheral mechanisms by blocking nicotine with the antagonists mecamylamine and hexamethonium. This project will compare different hypotheses for the effects of nicotine on responding for non-nicotine stimuli and will further validate an animal model for understanding the effects of nicotine on various environmental consequences.