g , Harris, Stepanov, Pentel, & Lesage, 2012) Human Testing: Bra

g., Harris, Stepanov, Pentel, & Lesage, 2012). Human Testing: Brain Imaging Brain imaging is one method of obtaining insight into the effects of RNC selleck Wortmannin cigarettes that may serve as an indicator of abuse liability. Several imaging techniques can be applied to study RNC cigarettes. Positron emission tomography (PET) can be used to determine the extent of occupancy of specific nicotinic receptor subtypes and the extent of dopamine release in certain regions of the brain in response to nicotine. For example, a ��2 PET ligand has been developed to determine the extent of occupancy and saturation of ��4��2 nicotinic cholinergic receptor (the receptor associated with the reinforcing effects of nicotine) in response to use of tobacco products.

Interestingly, studies have shown almost complete saturation of ��4��2 nicotinic acetylcholine receptors after smoking a single cigarette (Brody et al., 2006), whereas cigarettes with yields as low as 0.05mg nicotine have been found to occupy about 25% of the ��4��2 receptors (Brody, Mandelkern, Costello, et al., 2009). Likewise, studies have shown less striatal dopamine release when smoking 0.05-mg nicotine-yield cigarettes compared with normal nicotine-yield cigarettes (Brody, Mandelkern, Olmstead, et al., 2009). PET and MRI imaging techniques can be used to measure the effects of nicotine reduction on cerebral blood flow (Rose et al., 2003), activation in specific regions of the brain in response to tasks that assess cognition, craving, or mood states (Azizian, Monterosso, O��Neill, & London, 2009; Brody et al., 2002; Ernst et al.

, 2001; Tang et al., 2012; Wang et al., 2007), and brain connectivity (e.g., greater connectivity of the insula in nonsmokers vs. smokers; Ghahremani et al., 2011). However, research linking these brain effects to clinical features of nicotine addiction or reinforcement is needed. To date, little is known about the relationship between these brain measures and behavioral or subjective measures of nicotine addiction. Human Testing: Laboratory Models Accurate predictions of the effects of nicotine reduction is facilitated by a fundamental understanding of dose-effect relationships between unit dose and outcomes such as the physiological and subjective effects of smoking, symptoms of nicotine withdrawal, smoking topography, and pattern of smoking over time.

Methods for examining dose-effect relationships have been developed for both drugs (Carter Dacomitinib & Griffiths, 2009) and tobacco products (Carter et al., 2009). Researchers have already used similar techniques for assessing RNC products including measures of the following: (a) pharmacokinetics, subjective (e.g., drug liking), behavioral, and other responses (Benowitz, Jacob, & Herrera, 2006); (b) self-administration and puff topography (Kassel, Greenstein, et al.

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