Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics.
ABSTRACT Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior.
Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients.
We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded.
Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning.
This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.
SourceAvailable from: Lucy Alba-Ferrara[Show abstract] [Hide abstract]
ABSTRACT: Abstract Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executiveBrain Imaging and Behavior 04/2015; DOI:10.1007/s11682-015-9374-8 · 3.39 Impact Factor
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ABSTRACT: The endogenous opioid system is involved in the pathophysiology of alcohol-use disorders. Genetic variants of the opioid system alter neural and behavioral responses to alcohol. In particular, a single nucleotide polymorphism rs1799971 (A118G) in the mu-opioid receptor gene (OPRM1) is suggested to modulate alcohol-related phenotypes and neural response in the mesocorticolimbic dopaminergic system. Little is known about the clinical implications of these changes. The current study investigated the relationship of genotype effects on subjective and neural responses to alcohol cues and relapse in a sample of abstinent alcohol-dependent patients. Functional magnetic resonance imaging (fMRI) was used to investigate alcohol cue-reactivity and drinking outcome of 81 abstinent alcohol-dependent patients. G-allele carriers displayed increased fMRI cue-reactivity in the left dorsal striatum and bilateral insulae. Neural responses to alcohol cues in these brain regions correlated positively with subjective craving for alcohol and positive expectations of alcohol׳s effects. Moreover, alcohol cue-reactivity in the left dorsal striatum predicted time to first severe relapse. Current results show that alcohol-dependent G-allele carriers׳ increased cue-reactivity is associated with an increased relapse risk. This suggests that genotype effects on cue-reactivity might link the OPRM1 A118G risk allele with an increased relapse risk that was reported in earlier studies. From a clinical perspective, risk-allele carriers might benefit from treatments, such as neuro-feedback or extinction-based therapy that are suggested to reduce mesolimbic reactivity. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 04/2015; DOI:10.1016/j.euroneuro.2015.04.013 · 5.40 Impact Factor
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ABSTRACT: Prefrontal cortex (PFC) dysfunction is believed to contribute to the transition from controlled substance use to abuse. Because astrocytes have been suggested to play a key role in the development and maintenance of drug-seeking behaviors, we sought to determine whether PFC astrocytes are affected by ethanol (EtOH) self-administration. EtOH consumption was modeled in rats by 3 self-administration paradigms where EtOH was made concurrently available with water in the home cage either continuously (CEA) or intermittently (IEA). In the third paradigm, EtOH was only available in the operant chamber (OEA). To avoid the potential confound of acute EtOH effects, all rats were sacrificed after either 24-hour or 3-week abstinence. In all groups, the effect of EtOH consumption on PFC astrocytes was measured using unbiased stereological counting of cells expressing the astrocyte marker glial fibrillary acidic protein (GFAP). GFAP immunoreactivity commonly changes in response to pharmacological insult or injury. GFAP-positive astrocyte number increased in the prelimbic and anterior cingulate cortex regions of the PFC after IEA. No change was found in the infralimbic or orbitofrontal cortex after IEA. After 3-week abstinence, there was a reduction of astrocytes in the prelimbic and orbitofrontal cortex of the CEA cohort as well as a reduction in the orbitofrontal cortex of the OEA cohort. These findings demonstrate that discrete PFC subregions contain GFAP-positive astrocyte populations that respond differentially to distinct EtOH consumption paradigms. A better understanding of how specific astrocyte populations uniquely adapt to EtOH consumption could provide insight for targeted therapeutic interventions. Copyright © 2015 by the Research Society on Alcoholism.Alcoholism Clinical and Experimental Research 04/2015; 39(4):650-8. DOI:10.1111/acer.12683 · 3.31 Impact Factor