Extrastriatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder and Individuals at High Risk

Spitta, Gianna; Gleich, Tobias; Zacharias, Kristin; Butler, Oisín; Buchert, Ralph; Gallinat, Jürgen

doi:10.1159/000521103

Cited by 8 publications

(19 citation statements)

References 61 publications

(111 reference statements)

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“…Taken together, most PET studies reveal significant reductions in striatal dopamine D2/3 receptor availabilities among recently detoxified persons with AD, compared to HCs, which is consistent with findings of reviews and meta-analyses on in vivo PET studies [8, 9, 11, 28, 72]. This finding is consistent with findings from a series of studies showing a blunted dopamine D2 receptor availability in active alcohol users [33, 73] but not in persons with a longer duration of abstinence [49, 51]. Some animal models even suggest that recovery of DA neurotransmission during prolonged abstinence leads to a hyperdopaminergic state [74].…”

Section: Pet Imaging In Audsupporting

confidence: 87%

“…Additional variability results from using unilateral ROIs, separately in each brain hemisphere versus using bilateral ROIs, averaging the imaging signal in the considered ROI over both hemispheres. Compared to bilateral analyses, unilateral ROIs double the number of analyses and, therefore, require that statistical issues associated with multiple testing are addressed particularly carefully [33]. Strict application of Bonferroni correction might not be most appropriate for this purpose, particularly when the considered ROIs are not independent [33, 34, 44].…”

Section: Confounders Associated With Pet and Spect Methodologymentioning

confidence: 99%

“…However, in four studies, no DA releasing effect of alcohol administration was reported [28, 29, 31, 32]. Two of these studies focused their investigation on the extrastriatal (mostly prefrontal) brain regions [28, 29, 33–35] instead of the striatal regions, which may have contributed to these results. In any case, the strongest effects were observed in the ventral striatum/nucleus accumbens [21–23, 25, 30], which is consistent with findings from animal studies [18].…”

Section: Acute Dopamine Release After Alcohol Intakementioning

confidence: 99%

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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: Pet Imaging In Audsupporting

confidence: 87%

Section: Confounders Associated With Pet and Spect Methodologymentioning

confidence: 99%

Section: Acute Dopamine Release After Alcohol Intakementioning

confidence: 99%

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

Spitta,

Garbusow,

Buchert

et al. 2023

Neuropsychobiology

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“…In principle, this approach could also be expanded on to assess neuroadaptations to other drugs of abuse. For example, acute and chronic alterations in neurotransmission and functional connectivity of the mesocorticolimbic circuit have been reported for cocaine ( 69 – 71 ), nicotine ( 72 – 76 ), and alcohol ( 77 – 80 ). The current proposal on how to assess and define neuroadaptations in cannabis users would also call for an international, multi-center research effort in order to include large samples of distinct cannabis user groups, ranging from novice and occasional users at the lowest end of the use frequency spectrum to daily, chronic users at the opposite extreme.…”

Section: Discussionmentioning

confidence: 99%

Cannabis Use and Neuroadaptation: A Call for Δ9-Tetrahydrocannabinol Challenge Studies

et al. 2022

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Currently, the assessment of the neurobehavioral consequences of repeated cannabis use is restricted to studies in which brain function of chronic cannabis users is compared to that of non-cannabis using controls. The assumption of such studies is that changes in brain function of chronic users are caused by repeated and prolonged exposure to acute cannabis intoxication. However, differences in brain function between chronic cannabis users and non-users might also arise from confounding factors such as polydrug use, alcohol use, withdrawal, economic status, or lifestyle conditions. We propose a methodology that highlights the relevance of acute Δ9-tetrahydrocannabinol (THC) dosing studies for a direct assessment of neuroadaptations in chronic cannabis users. The approach includes quantification of neurochemical, receptor, and functional brain network changes in response to an acute cannabis challenge, as well as stratification of cannabis using groups ranging from occasional to cannabis-dependent individuals. The methodology allows for an evaluation of THC induced neuroadaptive and neurocognitive changes across cannabis use history, that can inform neurobiological models on reward driven, compulsive cannabis use.

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“…This special issue starts with an article of Sebold et al [7], who summarize computational theories on reinforcement learning to explain core symptoms of alcohol use disorders. With respect to neurobiological correlates of symptoms of drug addiction, Spitta et al [8] describe alterations in extrastriatal dopamine neurotransmission and their association with symptom severity in patients with alcohol use disorder and at-risk populations. Mechanisms and functions of goal-directed versus habitual behavior are discussed by Doñamayor et al [9] with a focus on contextual and personal factors.…”

mentioning

confidence: 99%