Dopamine and opioid systems adaptation in alcoholism revisited: Convergent evidence from positron emission tomography and postmortem studies

Hansson, Anita C.; Gründer, Gerhard; Hirth, Natalie; Noori, Hamid; Spanagel, Rainer; Sommer, Wolfgang

doi:10.1016/j.neubiorev.2018.09.010

Cited by 38 publications

(25 citation statements)

References 311 publications

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“…Interestingly and in line with the restricted expression pattern of D3 receptors, SB‐277011‐a modulated Acb connectivity differentially in PD and ND rats. This effect could be due to the dysregulation of dopaminergic striatal systems observed in alcohol exposed rats during protracted withdrawal as well as in AUD patients . Furthermore, SB‐277011‐a partially restored aberrant connectivity in PD rats but had no significant effects in alcohol‐naive rats.…”

Section: Discussionmentioning

confidence: 99%

Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade

et al. 2019

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A few studies have reported aberrant functional connectivity in alcoholic patients, but the specific neural circuits involved remain unknown. Moreover, it is unclear whether these alterations can be reversed upon treatment. Here, we used functional MRI to study resting state connectivity in rats following chronic intermittent exposure to ethanol. Further, we evaluated the effects of SB-277011-a, a selective dopamine D3 receptor antagonist, known to decrease ethanol consumption. Alcohol-dependent and control rats (N = 13/14 per group), 3 weeks into abstinence, were administered SB-277011-a or vehicle before fMRI sessions. Resting state connectivity networks were extracted by independent component analysis. A dual-regression analysis was performed using independent component maps as spatial regressors, and the effects of alcohol history and treatment on connectivity were assessed. A history of alcohol dependence caused widespread reduction of the internal coherence of components. Weaker correlation was also found between the insula cortex (IC) and cingulate cortices, key constituents of the salience network. Similarly, reduced connectivity was observed between a component comprising the anterior insular cortex, together with the caudate putamen (CPu-AntIns), and the posterior part of the IC. On the other hand, postdependent rats showed strengthened connectivity between salience and reward networks. In particular, higher connectivity was observed between insula and nucleus accumbens, between the ventral tegmental area and the cingulate cortex and between the VTA and CPu-AntIns. Interestingly, aberrant connectivity in postdependent rats was partially restored by acute administration of SB-277011-a, which, conversely, had no significant effects in naïve rats.

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Section: Discussionmentioning

confidence: 99%

Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade

et al. 2019

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“…On the other hand, the higher activation in the insula in individuals with higher severity of AUD and ADHD may also represent a compensatory mechanism, since the insula is also responsible for selfawareness and interoception (Eckert et al, 2009). Striatal dopaminergic states (either hypo-or hyperdopaminergic) may also serve as a link between and common mechanistic explanation for AUD and ADHD as well as impulsivity and cue reactivity (Hansson et al, 2019;Hirth et al, 2016;Volkow et al, 2009;Wiers et al, 2018), but further studies investigation this potential relation are needed.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, Hirth et al (2016) found a hyperdopaminergic state associated with protracted abstinence, which has in other contexts also been associated with a risk for increased impulsivity and eventual relapse. A recent review has generated further support for this theory of dynamic regulation and change in striatal dopaminergic signaling over the course of the addiction life-cycle, highlighting a potential source for the variability in findings on dopaminergic signaling in addiction to date (Hansson et al, 2019). A negative association, i.e.…”

Section: Introductionmentioning

confidence: 99%

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder

et al. 2020

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Rationale Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cuereactivity. Objectives In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cuereactivity with a hybrid imaging task. Methods Out of 69 adult study participants, we included n = 49 in our final analyses: Individuals had a diagnosis of either AUD (n = 13), ADHD (n = 14) or both (n = 5), or were healthy controls (HC; n = 17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cuereactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. Results The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. Conclusions Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

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“…Also, alcohol’s known actions on the dopamine system have been targeted many times, with negative or even detrimental outcomes in all these trials (reviewed in ref. 14 ). It has become clear that, without the ability to determine the specific state of an individual’s dopamine system and its responsivity, direct pharmacological interference with DA receptors and transporters is unlikely to succeed as a viable treatment approach.…”

Section: A Translational Crisismentioning

confidence: 99%

Developing neuroscience-based treatments for alcohol addiction: A matter of choice?

et al. 2019

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Excessive alcohol use is the cause of an ongoing public health crisis, and accounts for ~5% of global disease burden. A minority of people with recreational alcohol use develop alcohol addiction (hereafter equated with “alcohol dependence” or simply “alcoholism”), a condition characterized by a systematically biased choice preference for alcohol at the expense of healthy rewards, and continued use despite adverse consequences (“compulsivity”). Alcoholism is arguably the most pressing area of unmet medical needs in psychiatry, with only a small fraction of patients receiving effective, evidence-based treatments. Medications currently approved for the treatment of alcoholism have small effect sizes, and their clinical uptake is negligible. No mechanistically new medications have been approved since 2004, and promising preclinical results have failed to translate into novel treatments. This has contributed to a reemerging debate whether and to what extent alcohol addiction represents a medical condition, or reflects maladaptive choices without an underlying brain pathology. Here, we review this landscape, and discuss the challenges, lessons learned, and opportunities to retool drug development in this important therapeutic area.

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Dopamine and opioid systems adaptation in alcoholism revisited: Convergent evidence from positron emission tomography and postmortem studies

Cited by 38 publications

References 311 publications

Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade

Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade

Interaction between behavioral inhibition and neural alcohol cue-reactivity in ADHD and alcohol use disorder

Developing neuroscience-based treatments for alcohol addiction: A matter of choice?

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