However, the specific role for nicotine in these reinforcing effects is still unclear because of the difficulties performing intravenous nicotine self-administration in humans. Acutely, cigarette smoking is reported to induce positive reinforcing effects, including mild euphoria, heightened arousal, reduced appetite, and reduced stress, anxiety, and pain ( Pomerleau et al., 1984 Pomerleau and Pomerleau, 1992 Stolerman and Jarvis, 1995). The rate of absorption of smokeless tobacco products, with the exception of electronic cigarettes, is considerably slower (30 min to reach maximum blood levels), accounting for a lower abuse potential for these products ( Benowitz et al., 1988). Nicotine rapidly enters the pulmonary venous circulation, reaches the brain within 10–20 s, and readily diffuses into brain tissue where it binds to nicotine acetylcholine receptors (nAChRs Benowitz et al., 1988). Cigarettes typically contain 10–14 mg of nicotine ( Kozlowski et al., 1998), of which 1–1.5 mg is absorbed systemically in the lungs through inhalation ( Armitage et al., 1975 Benowitz and Jacob, 1984). The primary psychoactive ingredient responsible for tobacco use is nicotine ( Cummings and Mahoney, 2006), although tobacco smoke also contains more than 4,000 additional chemicals, many of which have psychoactive properties or may act in concert with nicotine to contribute to smoking dependence ( Clemens et al., 2009 Hoffman and Evans, 2013). The rapid growth of electronic cigarette use worldwide ( Caponnetto et al., 2012) is also an important health concern that requires the development of novel animal models of exposure to nicotine vapor. However, chewing tobacco, dry snuff, and moist snuff are a concern in certain countries ( Bhattacharyya, 2012 Giovino et al., 2012). Cigarette smoking appears to be more central to the epidemiology of nicotine addiction compared with smokeless tobacco abuse. According to a recent review ( Giovino et al., 2012), 24% of the United States population older than 15 years of age are cigarette smokers, and 1.8% are smokeless tobacco users.
Tobacco use is the leading cause of preventable disease and premature death, leading to 440,000 deaths annually in the United States alone ( Fellows et al., 2002). Features of Tobacco Smoking, Nicotine Abuse, and Dependence in Humans The last section discusses how these different animal models can be used to investigate the neurobiological mechanisms that mediate nicotine reinforcement and dependence. We then discuss the limits and advantages of the most used animal models of nicotine use and dependence and novel animal models of escalated nicotine intake and exposure to nicotine vapor. In this review, we first describe the features of tobacco smoking and nicotine abuse and dependence in humans.
Studies on the neurobiological substrates of tobacco addiction largely depend on the availability of suitable animal models. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use, and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure.
Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.