Russell et al. suggested that the relative reduction of plasma nicotine spikes in heavy smokers http://www.selleckchem.com/products/AP24534.html is to avoid any drop in nicotine, which will cause discomfort or other negative effects. In contrast, the rapid peaks (boosts) in nicotine in regular smokers are positively reinforcing. They also concluded that a venous blood nicotine boost of 10 ng/ml per tobacco cigarette is sufficient for positive subjective effects. A similar boost in venous plasma nicotine produces electroencephalographic changes consistent with increased arousal (Kadoya, Domino, & Matsuoka, 1994). Such a nicotine boost can also be obtained from oral and nasal snuff or nasal spray but as rapidly as other forms, such as nicotine gum and patches. Russell et al.

(1980) suggested in very heavy smokers reinforcement through withdrawal relief, in contrast to light smokers where positive reinforcement to nicotine boost occurs. In light tobacco smokers, there is a positive correlation between the number of cigarettes smoked and plasma nicotine, whereas there is little correlation in heavy tobacco smokers. Similar findings were reported by Gori and Lynch (1985) using a much larger sample. Besides nicotine, the major pharmacologically active ingredient, there are many other chemicals in tobacco smoke (Bernhard, 2011; Layten-Davis & Nielson, 1999; Rodgman & Perfetti, 2008; Schmeltz, 1995). Fowler, Volkow, Wang, Pappas, Logan, MacGregor, et al. (1996) and Fowler, Volkow, Wang, Pappas, Logan, Shea, et al. (1996) reported that tobacco smoke inhibits brain monoamine oxidase A and B, but exactly what chemical is responsible is still unclear.

Clemens et al. (2009) found five minor tobacco alkaloids that increase rat nicotine locomotor activity and nicotine self-administration. Rodd-Henricks et al. (2002) described the reinforcing effects of acetaldehyde (also in tobacco smoke) in the posterior tegmental area of alcohol preferring rats. Presumably, all of these substances are present equally in the smoke of the denic as well as nic cigarettes used and could be one explanation of the effects of denic tobacco smoking. Another could be the psychological cues surrounding cigarettes and other addictive substances that acquire value. This is central to many theories of addiction, most notably the incentive sensitization theory of addiction of Robinson and Berridge (1993). In real world situations, Cilengitide there are cues that surround and pervade the life of smokers such as time breaks, advertisements, etc. Cues are strongly linked to the maladaptive behavior of addicts to many different substances including tobacco (Berridge, 2000, 2007; Flagel, Akil, & Robinson, 2009; Jansen, 1998).