Baclofen-Induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure. Methods: In this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving. Results: Whole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (pFWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (pFWEcorr ＜ 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02). Conclusion: Results suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse

Alcohol-induced fragmentary blackouts : associated memory processes and neural correlates

textAlcohol-induced blackouts, or periods of anterograde amnesia without loss of consciousness, were a diagnostic indicator in Jellinek’s (1952) theory of alcoholism and have been correlated with alcohol use problems (Campbell & Hodgins, 1993; Goodwin, Crane, & Guze, 1969; Ryback, 1970; Tarter & Schneider, 1976). Other findings suggest that blackouts are a warning sign of problem drinking, but not a predictor of alcohol use disorders (Anthenelli, Klein, Tsuang, Smith, & Schuckit, 1994). Most published research on blackouts focuses on cognitive deficits among older alcohol-dependent adults, yet recent research indicates prevalence rates for blackouts as high as 50% among college students (White, Jamieson-Drake, & Swartzwelder, 2002). In addition, young adults who reported experiencing a blackout were later told that they had vandalized property, driven a car, or engaged in other risky behaviors without remembering (Buelow & Koeppel, 1995). Despite their high prevalence and associated negative consequences, relatively little is known about alcohol-induced blackouts or their neural, social, and behavioral correlates among non-dependent populations. The current research explored individual variation in memory functioning under sober and intoxicated conditions and alcohol’s effects on neural activation during memory processes.Psycholog

Perceived anonymity and alcohol use by high school and college students

Perceived anonymity, or beliefs about how much parents and peers know and care about students’ behavior, was assessed in relation to their drinking patterns. Prior to and after leaving for college, students completed web-based surveys assessing alcohol use, family and social motives, and perceived anonymity from parents and peers. Family motives moderated the effect of perceived parental anonymity on high school alcohol use, whereas peer motives moderated the effect of perceived peer anonymity on college drinking. Longitudinally, college drinking increased as individuals moved from low perceived anonymity in high school to high perceived anonymity in college. Perceived anonymity is a possible mechanism through which parents exert influence during high school whereas peers are more influential in college.Psycholog

A longitudinal examination of adolescent response inhibition: neural differences before and after the initiation of heavy drinking.

RationaleResponse inhibition abnormalities contribute to several maladaptive behaviors commonly observed during adolescence, including heavy drinking.ObjectivesThe present study aimed to determine whether abnormalities in brain response during response inhibition predate or follow adolescents' transition into heavy drinking, which is pivotal in identifying the neural antecedents and consequences of adolescent alcohol use.MethodsLongitudinal functional magnetic resonance imaging (fMRI) acquired during a response inhibition task was collected on adolescents before the onset of heavy drinking and then again on the same scanner approximately 3 years later. Adolescents who transitioned into heavy drinking (n = 20) were matched to continuously nondrinking adolescents (n = 20) on baseline and follow-up demographic and developmental variables.ResultsDuring no-go relative to go trials, participants showed responses common to inhibitory circuitry: frontal (e.g., pre-supplementary motor area), temporal, and parietal regions. A repeated measures analysis of covariance revealed that adolescents who later transitioned into heavy drinking showed less fMRI response contrast at baseline than continuous nondrinkers in frontal, parietal, subcortical, and cerebellar regions (p < 0.01, clusters >756 μl), then increased activation after the onset of heavy drinking in frontal, parietal, and cerebellar areas.ConclusionsFuture heavy drinkers showed less activation of inhibitory circuitry before the onset of heavy drinking. After transitioning into heavy drinking, they showed more activation during response inhibition than nondrinking controls. These results contribute to the growing literature suggesting that neural vulnerabilities exist prior to the onset of substance use, and the initiation of heavy drinking may lead to additional alterations in brain functioning