Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study

Joo, Yung Hyup; Kim, Jeong-Hee; Kim, Hang-Keun; Son, Young-Don; Cumming, Paul; Kim, Jong-Hoon

doi:10.3390/life11060506

Cited by 5 publications

(5 citation statements)

References 73 publications

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“…Interestingly, Maillard et al [176] found a hypermetabolism in the cerebellum and hippocampus of persons with AD who relapsed within 6 months and additionally in the anterior cingulate cortex of persons with AD who relapsed after 12 months. Further (preclinical) multimodal studies combining PET and MRI in AD investigated glutamatergic but not DA neurotransmission in animal models [177, 178].…”

Section: Correlations With Other Imaging Results (Fmri Mrs)mentioning

confidence: 99%

Dopamine and Alcohol: A Review of in vivo PET and SPECT Studies

Spitta,

Garbusow,

Buchert

et al. 2023

Neuropsychobiology

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Background: Alcohol-associated alterations of the dopaminergic (DA) system have been investigated via functional single-photon emission tomography (SPECT) positron emission tomography (PET) and imaging methods over many years, investigating presynaptic or postsynaptic markers, such as DA receptor and DA transporter availability, both with and without challenge. This review summarizes SPECT and PET studies on different levels of alcohol consumption to support the dimensional view of alcohol use disorder (AUD), ranging from acute consumption in social drinkers, individuals at high risk to patients with severe AUD and their association with blunted DA neurotransmission. Additionally, confounding factors of PET and SPECT studies of the DA system were discussed. Summary: The included studies provided strong evidence that acute alcohol administration in social drinkers is followed by a DA release, particularly in the ventral striatum. In participants with AUD, DA release appears to be impaired as administration of a psychostimulant is followed by a blunted striatal DA. Furthermore, in recently detoxified participants with AUD, in vivo dopamine D2 and D3 receptor availability appears to be reduced, which may be a predisposing factor or the result of a neuroadaptive process influencing drug-induced DA release. DA transporter availability is reduced in AUD, whereas findings with respect to DA synthesis capacity are controversial. Key Messages: The DA system seems to be differently impaired during the development and persistence of AUD. In total, challenge studies (acute alcohol or psychostimulant administration) seem to be more consistent in their findings and might be less prone to the effects of confounders. Long-term studies with larger samples are required to better evaluate the alterations during chronic consumption and prolonged abstinence.

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Section: Correlations With Other Imaging Results (Fmri Mrs)mentioning

confidence: 99%

Dopamine and Alcohol: A Review of in vivo PET and SPECT Studies

Spitta,

Garbusow,

Buchert

et al. 2023

Neuropsychobiology

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“…Despite numerous differences in the study populations, taken together this suggests that the higher mGlu5 receptor availability identified in the present sample may be characteristic of an early abstinence period. Thus the 4‐week time point may not have been long enough to observe significant change (Camchong et al, 2013b; Joo et al, 2021). Smoking may also influence these relationships given its effects on mGlu5 receptor availability; though there were no significant effects of smoking on connectivity outcomes or PET‐fMRI relationships in these analyses, the power to detect these was limited.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, there is little evidence in these data that connectivity differences change toward control levels within the first month of abstinence. However, a report of mGlu5 receptor availability and functional connectivity in men with AUD (67% smokers) abstinent from alcohol >2 years identified clusters of lower BP ND in the abstinent AUD group in temporal and parietal cortices compared to healthy controls (Joo et al, 2021). Seed‐based analyses identified an area in the parietal cortex with lower mGlu5 availability in the AUD patients that also had higher functional connectivity with occipital cortex compared to healthy controls, while network and global connectivity were not evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…This is generally consistent with previous studies (Akkus et al, 2018; Ceccarini et al, 2020; Kupila et al, 2013; Laukkanen et al, 2019; Leurquin‐Sterk et al, 2018), although tobacco smoking likely interacts with this effect (Ceccarini et al, 2020; Leurquin‐Sterk et al, 2018). The relationship between functional connectivity alterations and mGlu5 receptor availability in AUD during early abstinence has not yet been investigated, though prior work demonstrates that these co‐occur (Joo et al, 2021). Directly comparing these two systems could help elucidate relationships between molecular and neural pathways implicated in AUD.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Multimodal neuroimaging of metabotropic glutamate 5 receptors and functional connectivity in alcohol use disorder

Smart

Worhunsky

Scheinost

et al. 2022

Alcoholism Clin & Exp Res

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Background People recovering from alcohol use disorder (AUD) show altered resting brain connectivity. The metabotropic glutamate 5 (mGlu5) receptor is an important regulator of synaptic plasticity potentially linked with synchronized brain activity and a target of interest in treating AUD. The goal of this work was to assess potential relationships of brain connectivity at rest with mGlu5 receptor availability in people with AUD at two time points early in abstinence. Methods Forty‐eight image data sets were acquired with a multimodal neuroimaging battery that included resting‐state functional magnetic resonance imaging (fMRI) and mGlu5 receptor positron emission tomography (PET) with the radiotracer [18F]FPEB. Participants with AUD (n = 14) were scanned twice, at approximately 1 and 4 weeks after beginning supervised abstinence. [18F]FPEB PET results were published previously. Primary comparisons of fMRI outcomes were performed between the AUD group and healthy controls (HCs; n = 23) and assessed changes over time within the AUD group. Relationships between resting‐state connectivity measures and mGlu5 receptor availability were explored within groups. Results Compared to HCs, global functional connectivity of the orbitofrontal cortex was higher in the AUD group at 4 weeks of abstinence (p = 0.003), while network‐level functional connectivity within the default mode network (DMN) was lower (p < 0.04). Exploratory multimodal analyses showed that mGlu5 receptor availability was correlated with global connectivity across all brain regions (HCs, r = 0.41; AUD group at 1 week of abstinence, r = 0.50 and at 4 weeks, r = 0.46; all p < 0.0001). Furthermore, a component of cortical and striatal mGlu5 availability was correlated with connectivity between the DMN and salience networks in HCs (r = 0.60, p = 0.003) but not in the AUD group (p > 0.3). Conclusions These preliminary findings of altered global and network connectivity during the first month of abstinence from drinking may reflect the loss of efficient network function, while exploratory relationships with mGlu5 receptor availability suggest a potential glutamatergic relationship with network coherence.

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“…Antagonism of the metabotropic GLU receptor, mGluR5, prevented alcohol induced relapse in rats ( Adams, Short, & Lawrence, 2010 ). Recent advances using positron emission tomography (PET) imaging have identified a link between mGluR5 availability (specifically cortical and mesolimbic) and long-term relapse in patients who abuse alcohol ( Ceccarini et al, 2020 ; Joo et al, 2021 ). Additionally, acute alcohol use inhibits the ionotropic GLU receptor NMDAR while chronic alcohol use upregulates NMDAR function.…”

Section: Alcoholmentioning

confidence: 99%