Indeed, consideration of how a nicotine reduction policy might be

Indeed, consideration of how a nicotine reduction policy might be implemented raises important questions about the temporal aspects of reduction (e.g., gradual versus abrupt reduction). Benowitz and Henningfield (1994) originally recommended a reduction in nicotine levels of all cigarettes over the course of 10�C15 years, although selleck chem MEK162 recent studies have demonstrated that immediate reduction is also successful in decreasing smoking and even dependence (Donny, Houtsmuller, & Stitzer, 2007; Hatsukami et al., 2010). While arguments could be made for either reduction strategy, the rate of reduction may substantially impact the level to which nicotine content would need to be reduced.

Although no studies to date have addressed this issue, early work on nicotine self-administration did find that rats switched to saline extinguished more slowly if they received an intermediate dose reduction prior to saline substitution (Cox et al., 1984). Future animal research should directly assess the impact of different temporal parameters to better determine whether the reinforcement threshold depends on the rate at which nicotine is reduced and other interacting variables (e.g., cues). Other Outcome Measures Compensation One major concern about a nicotine reduction policy is that smokers might compensate for reduced nicotine levels by smoking more cigarettes and/or smoking more intensely as the nicotine content in products is reduced. Consequently, exposure to tobacco toxins would be, at least transiently, increased.

Compensation is commonly observed when smokers switch to cigarettes with a lower nicotine and tar yield or reduce the number of cigarettes they smoke per day (Hecht et al., 2004; Scherer, 1999). A marked degree of variability between subjects is evident in many of these studies, ranging from no compensation to near complete compensation. Understanding the mechanisms underlying these individual differences in compensation is critical for predicting which populations are at greatest risk for compensation and in need of interventions to minimize it. Despite the importance of compensatory smoking in humans, this phenomenon has received little direct attention in animal nicotine self-administration models. Numerous studies have shown that modest compensatory increases in nicotine self-administration occur when the unit dose is reduced from a relatively high training dose (60 ��g/kg; Shoaib et al.

, 1997; Watkins et al., 1999). As in human smokers, individual differences in compensation are observed in rats self-administering nicotine; however, few have paid specific attention to factors that moderate individual Anacetrapib differences in compensation (Harris, Burroughs, Pentel, & LeSage, 2008; Harris, Pentel, Burroughs, Staley, & Lesage, 2011; Harris, Pentel, & LeSage, 2009).

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