The effects of repeated exposure on the reward-enhancing effects of nicotine Scott T. Barrett a and Amy L. Odum b Nicotine increases operant responding for a weakly reinforcing audiovisual stimulus in rats, but the role of repeated exposure in the development of this effect has not been explicitly investigated. This study investigated, in two experiments, whether repeated nicotine exposure is a requisite for the expression of a reward-enhancing effect in rats, using a probe design by administering nicotine acutely at a range of doses (0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg) both before and after two weeks of daily administration of 0.3 mg/kg of nicotine. Nicotine did not enhance responding for an audiovisual stimulus relative to baseline at any dose when administered before repeated daily administration, but responding was enhanced at 0.1, 0.3, and 1.0 mg/kg of nicotine after daily administration. The results suggest that repeated exposure to nicotine is a requisite for the expression of reward-enhancing effects, and implicate sensitization to the effects of nicotine in this process. Behavioural Pharmacology 22:283–290  c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Behavioural Pharmacology 2011, 22:283–290 Keywords: nicotine, rats, reward enhancement a Department of Psychology, University of Nebraska-Lincoln, Lincoln, Nebraska and b Department of Psychology, Utah State University, Logan, Utah, USA Correspondence to Scott T. Barrett, BS, Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, Nebraska, 68588, USA E-mail: s.taylor.barrett@gmail.com Received 27 January 2011 Accepted as revised 28 February 2011 Introduction Tobacco use is one of the largest contributors to the global burden of disease in addition to being the most prevalent form of drug abuse (World Health Organization, 2004). Research suggests that nicotine is the primary addictive component of tobacco and that nicotine reinforcement is largely responsible for the acquisition and maintenance of tobacco use (United States Depart- ment of Health and Human Services, 1988). Nicotine reinforcement is at present believed to result from three characteristics of nicotine: (i) its ability to act as a weak, primary (innate) reinforcer; (ii) its ability to create secondary reinforcers out of temporally associated, non- pharmacological stimuli; and (iii) its ability to enhance through nonassociative means the already present re- inforcement value of other, nonpharmacological stimuli (Chaudhri et al., 2006a, 2006b). The combination and interaction of these three sources of nicotine reinforce- ment are likely what makes tobacco use so addictive and difficult to terminate (Bevins and Palmatier, 2004). The finding that nicotine enhances the reinforcement value of other rewarding stimuli is relatively new and has sparked considerable interest as it seems to fill an important gap in the understanding of nicotine reward. Nicotine, by itself, seems to be a relatively weak primary reinforcer as evidenced by the difficulties in establishing reliable nicotine self-administration in the laboratory (Caggiula et al., 2002; Chaudhri et al., 2006a, 2006b). However, the effect of nicotine to enhance other rewarding stimuli seems rather robust and has implications for the social nature of tobacco use. One of the most striking examples of the reward- enhancement effect of nicotine are the results of several experiments conducted by Donny et al. (2003), which indicate that rats will lever press at substantially higher rates for a weakly-reinforcing visual stimulus when adminis- tered nicotine infusions. Across four groups, rats received either response dependent or response-independent nico- tine, and either response-dependent visual stimulus pre- sentation or no stimulus presentation. After prolonged exposure to these arrangements, response rates were highest in the groups that received nicotine (either response dependent or response independent) and a response-dependent visual stimulus. Importantly, re- sponding did not differ significantly between groups receiving nicotine, indicating that the reinforcement- enhancing effects of nicotine were unrelated to whether nicotine infusions were response dependent (Donny et al., 2003). These results suggest that regardless of whether nicotine is self-administered or passively administered, it has the effect of substantially increasing the reinforce- ment value of other rewarding stimuli, without earlier establishment of those stimuli as conditioned reinforcers. This result has also been confirmed with continuous nicotine infusion, eliminating the possibility that the visual stimulus was in actuality a secondary reinforcer by virtue of accidental pairing with nicotine infusions (Donny et al., 2003). There is reason to believe that repeated exposure to nicotine is a requisite for the expression of this reward- potentiation effect. Two previous studies have investi- gated this issue. Palmatier et al. (2007a) treated rats with Original article 283 0955-8810  c 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/FBP.0b013e3283473c25 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.