Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

OBJECTIVE: The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. METHOD: Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. RESULTS: In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. CONCLUSIONS: In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.

Relationships Between Current and Past Binge Drinking and Systolic Blood Pressure in Young Adults.

PURPOSE: Heavy episodic (i.e., "binge") drinking (i.e., ≥five drinks/occasion) is highly prevalent among young adults; those who binge do so four times per month on average, consuming nine drinks on average on each occasion. Although it is well established that chronic heavy drinking (≥two alcoholic beverages per day) increases the risk of hypertension, the relationship between binge drinking and blood pressure is not well described. Our aim was to describe the relationship between frequency of binge drinking, both current (at age 24 years) and past (at age 20 years), and systolic blood pressure (SBP) at age 24 years. METHODS: Participants (n = 756) from the longitudinal Nicotine Dependence in Teens study reported alcohol consumption at ages 20 and 24 years and had SBP measured at age 24 years. We examined the association between binge drinking and SBP using multiple linear regression, controlling for sex, race/ethnicity, education, monthly drinking in high school, cigarette smoking, and body mass index. RESULTS: Compared to nonbinge drinkers, SBP at age 24 years was 2.61 [.41, 4.82] mm Hg higher among current monthly bingers and 4.03 [1.35, 6.70] mm Hg higher among current weekly bingers. SBP at age 24 years was 2.90 [.54, 5.25] mm Hg higher among monthly bingers at age 20 years and 3.64 [.93, 6.35] mm Hg higher among weekly bingers at age 20 years, compared to nonbinge drinkers. CONCLUSIONS: Frequent binge drinking at ages 20 and 24 years is associated with higher SBP at age 24 years and may be implicated in the development of hypertension.