Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerstrom test of nicotine
dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited Necrostatin-1 manufacturer greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.”
“Modulation of striatal dopamine
(DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive 8-Bromo-cAMP manufacturer effects of nicotine. Nicotine, by desensitizing beta 2 subunit-containing Tryptophan synthase (beta 2*) nicotinic acetylcholine receptors (nAChRs) on striatal DA axons, significantly enhances
how DA is released by reward-related burst activity compared to nonreward-related tonic activity. This action provides a synaptic mechanism for nicotine to facilitate the DA-dependent reinforcement. The subfamily of beta 2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of alpha 6 beta 2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real-time using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in mouse striatal slices. The alpha 6-specific antagonist alpha-conotoxin-MII suppressed DA release evoked by single and low-frequency action potentials and concurrently enhanced release by high-frequency bursts in a manner similar to the beta 2*-selective antagonist dihydro-beta-erythroidine (DH beta E) in NAc, but less so in CPu. The greater role for alpha 6*-nAChRs in NAc was not due to any confounding regional difference in ACh tone since elevated ACh levels (after the acetylcholinesterase inhibitor ambenonium) had similar outcomes in NAc and CPu. Rather, there appear to be underlying differences in nAChR subtype function in NAc and CPu.