Basal ganglia/limbic striatal and thalamocortical involvement in craving and loss of control in alcoholism

Jg, Modell; Jm, Mountz; Tp, Beresford

doi:10.1176/jnp.2.2.123

Cited by 67 publications

(6 citation statements)

References 195 publications

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“…Preclinical evidence indicates that chronic alcohol exposure may affect the basal ganglia network, and dysfunctions in this network may contribute to alcohol-related cognitive impairment 75 . Previous research also suggests that the basal ganglia network plays a role in alcohol craving and loss of control over alcohol consumption 76 . The GLP-1 system also interacts with the basal ganglia network.…”

Section: Discussionmentioning

confidence: 99%

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Farokhnia

Fede

Grodin

et al. 2022

Sci Rep

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Growing evidence suggests that the glucagon-like peptide-1 (GLP-1) system is involved in mechanisms underlying alcohol seeking and consumption. Accordingly, the GLP-1 receptor (GLP-1R) has begun to be studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The aim of this study was to investigate the association between genetic variation at the GLP-1R and brain functional connectivity, according to the severity of alcohol use. Participants were 181 individuals categorized as high-risk (n = 96) and low-risk (n = 85) alcohol use, according to their AUD identification test (AUDIT) score. Two uncommon single nucleotide polymorphisms (SNPs), rs6923761 and rs1042044, were selected a priori for this study because they encode amino-acid substitutions with putative functional consequences on GLP-1R activity. Genotype groups were based on the presence of the variant allele for each of the two GLP-1R SNPs of interest [rs6923761: AA + AG (n = 65), GG (n = 116); rs1042044: AA + AC (n = 114), CC (n = 67)]. Resting-state functional MRI data were acquired for 10 min and independent component (IC) analysis was conducted. Multivariate analyses of covariance (MANCOVA) examined the interaction between GLP-1R genotype group and AUDIT group on within- and between-network connectivity. For rs6923761, three ICs showed significant genotype × AUDIT interaction effects on within-network connectivity: two were mapped onto the anterior salience network and one was mapped onto the visuospatial network. For rs1042044, four ICs showed significant interaction effects on within-network connectivity: three were mapped onto the dorsal default mode network and one was mapped onto the basal ganglia network. For both SNPs, post-hoc analyses showed that in the group carrying the variant allele, high versus low AUDIT was associated with stronger within-network connectivity. No significant effects on between-network connectivity were found. In conclusion, genetic variation at the GLP-1R was differentially associated with brain functional connectivity in individuals with low versus high severity of alcohol use. Significant findings in the salience and default mode networks are particularly relevant, given their role in the neurobiology of AUD and addictive behaviors.

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Section: Discussionmentioning

confidence: 99%

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Farokhnia

Fede

Grodin

et al. 2022

Sci Rep

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“…The involvement of the dopaminergic limbic system (133) and the ‘incentive sensitization’ model of craving (55, 62) suggests that dopamine antagonists may counteract the DA moderated effects of alcohol intoxication (134). A RCT investigating the effect of the D 2 -antagonist haloperidol in alcohol-dependent individuals showed that pre-treatment with haloperidol significantly reduced alcohol craving, amount of alcohol ingested, and reduced impulsivity (134).…”

Section: Current Pharmacotherapy Treatments To Reduce Craving For mentioning

confidence: 99%

Pharmacological Approaches to Reducing Craving in Patients with Alcohol Use Disorders

2014

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Research on the concept of craving may lead to a better understanding of the biobehavioral circuitries that contribute to the complexity of Alcohol Use Disorders (AUD). The experiences described as craving or desire to drink, are often associated with physical responses such as increased salivation, heart rate and alteration of stress hormones as well as psychological responses such as anxiety and depression. Greater craving has been associated with the increased probability of alcohol relapse. Reversal of craving, understood as a symptom of protracted abstinence, offers the possibility of preventing relapses and treating alcoholism. Various medications have been studied to establish whether they are able to reduce craving; however, the results obtained from clinical studies have been inconsistent. Here we review the interdisciplinary models developed to evaluate craving, then the different approaches used to assess and measure craving, and finally, the medications utilized and tested to lessen craving in patients suffering from AUD.

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“…Modell, Mountz and Beresford (1990) proposed impaired control may be triggered by impairment of inhibitory mechanisms in the striatum resulting from acute dopamine release following alcohol use. Modell et al (1993) obtained some evidence supporting this position from a study of alcohol administration/self-administration following injection of the D2-like receptor antagonist haloperidol or saline in alcohol dependent individuals of varying ages who self-reported frequent impaired control.…”

Section: Relationships Between Impaired Control and Impulsivitymentioning

confidence: 99%

“…Little work has been done to relate impaired control directly to brain function or neurotransmitter systems, with the exception of Modell and colleagues’ work (1990; 1993) concerning relationships between dopaminergic function and impaired control. Research on impulsivity and research linking alcohol use to particular neurotransmitters or brain regions may help guide future research.…”

Section: Pertinent Research Questions Concerning Impaired Control Ovementioning

confidence: 99%

Impaired control over alcohol use: An under-addressed risk factor for problem drinking in young adults?

Leeman

Patock‐Peckham

Potenza

2012

Experimental and Clinical Psychopharmacology

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Impaired control over alcohol use may be defined as “a breakdown of an intention to limit consumption in a particular situation” (Heather, Tebbutt, Mattick, & Zamir, 1993, p. 701) and has long been considered an important feature of alcohol dependence. Evidence suggests impaired control is highly relevant to young adult problem drinking. In the natural history of problem drinking, impaired control tends to develop early and may predict alcohol-related problems prospectively in undergraduates. Impaired control over alcohol use may be a facet of generalized behavioral under-control specifically related to drinking. In particular, impaired control is theoretically and empirically related to impulsivity. The question of whether impaired control represents a facet of impulsivity or a related but separate construct requires further study. However, theoretical arguments and empirical evidence suggest that there are unique qualities to the constructs. Specifically, existing data suggest that self-report measures of impaired control and impulsivity over alcohol use relate distinctly to problem drinking indices in young adults. Several lines of future research concerning impaired control are suggested, using the impulsivity literature as a guide. We conclude that impaired control is a valuable construct to the study of young adult problem drinking and that measures of impaired control should be included in more young adult alcohol studies. The extent to which impaired control over the use of other substances and impaired control over engagement in other addictive behaviors are clinically relevant constructs requires additional study.

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Basal ganglia/limbic striatal and thalamocortical involvement in craving and loss of control in alcoholism

Cited by 67 publications

References 195 publications

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Pharmacological Approaches to Reducing Craving in Patients with Alcohol Use Disorders

Impaired control over alcohol use: An under-addressed risk factor for problem drinking in young adults?

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