| Smoking and tobacco dependence are serious health concerns in the United States and globally. Reward via the pharmacological effects of nicotine are believed to be the principal motivating factor that drive tobacco dependence. Research reveals differences in sensitivity between males and females to the motivational effects of nicotine in tobacco use. Enhancement of reinforcement value of non-nicotine rewards contributes to overall nicotine reward. Similar value-enhancing effects have been observed by the two most commonly prescribed smoking cessation aids, bupropion and varenicline. The present dissertation investigated the value-enhancing effects of nicotine, bupropion and varenicline in both male and female rats using a behavioral economic, reinforcer demand approach. Additionally, the role of dopamine D1 and D2 receptor families and of &agr;4beta2* and &agr;7 nicotinic acetylcholine receptors (nAChRs) were investigated in the enhancing effects of nicotine and of bupropion and varenicline, respectively. In two experiments, rats were trained to lever-press maintained by visual stimulus (VS) reinforcement. The response requirement was systematically increased over blocks of 16 sessions according to the following sequence of fixed ratio schedules: 1, 2, 4, 8, 16, 32, 64, 128, 256, 512. Saline, nicotine and bupropion (Experiment 1) or varenicline (Experiment 2) were administered preceding sessions within each session block. Demand for VS reinforcement was analyzed under each drug condition and between the sexes using a behavioral economic model. The effects of dopamine (D1 or D2 family, Exp1) or nAChR antagonism (&agr;4beta2* and &agr;7, Exp2) under each drug condition were also analyzed on responding maintained by progressive ratio VS reinforcement. Nicotine, bupropion and varenicline each enhanced the value of VS reinforcement in male and female rats. Females showed greater sensitivity to the value-enhancing effects of each drug, especially on measures of persistence. Enhancement by bupropion but not nicotine was attenuated by D2 family antagonism in both sexes. Antagonism of &agr;4beta2* but not &agr;7 nAChRs attenuated the value-enhancing effects of nicotine and varenicline in females, but only of nicotine in males. |
