Mechanisms by which Nicotine Enhances Pavlovian Approach Behavior and Responding for a Conditioned Reinforcer

Tobacco dependence is among the leading causes of preventable deaths in North America. The main psychoactive ingredient contributing to the addictive properties of tobacco is nicotine. Nicotine use may be reinforced, in part, by an effect of nicotine to enhance the motivating properties of reward-associated stimuli. This effect can be measured in animals by first pairing a discrete stimulus with primary reinforcement in a Pavlovian conditioning procedure, making the cue a conditioned stimulus (CS). To assess the motivating properties of that CS, a second step is employed to assess the ability of the CS to serve as a conditioned reinforcer and support a novel, operant response. The number of responses performed for presentations of the CS as a conditioned reinforcer is enhanced by psychostimulant drugs, such as nicotine. In this thesis, I found that the administration of nicotine during Pavlovian conditioning enhances approach behavior towards the reward delivery receptacle when the CS indicates reward availability. This phenomenon occurred in two different Pavlovian conditioning procedures. In the second step, those animals that received nicotine injections during the Pavlovian conditioning phase displayed enhanced responding for the Pavlovian CS as a conditioned reinforcer under the influence of an acute nicotine injection. To further characterize this effect of nicotine on the reinforcing properties of CSs, I identified the specific nicotinic receptor subtypes involved in this effect, examined the longevity of responding for conditioned reinforcement, and assessed the ability of nicotine and the cues to reinvigorate this operant response after extinguishing such behavior. Furthermore, I found that drugs that act on dopamine (DA) or serotonin (5-HT) receptors modify the effect of nicotine to enhance motivated responding for conditioned reinforcement. Finally, I assessed the impact of administering varenicline, bupropion, lorcaserin, and naltrexone on nicotine-enhanced responding for a conditioned reinforcer. Together, these data substantiate a role for nicotine in enhancing the motivating properties of CSs, and identify several pharmacological targets that influence this property of nicotine reinforcement.Ph.D