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. 2018 Jul;3(7):591-598.
doi: 10.1016/j.bpsc.2018.03.018. Epub 2018 Apr 21.

Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder

Lawrence S Kegeles  1 , Guillermo Horga  2 , Rassil Ghazzaoui  2 , Rachel Rosengard  2 , Najate Ojeil  2 , Xiaoyan Xu  2 , Mark Slifstein  2 , Ismene Petrakis  3 , Stephanie S O'Malley  3 , John H Krystal  3 , Anissa Abi-Dargham  4
Affiliations

Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder

Lawrence S Kegeles et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Jul.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jan;5(1):130. doi: 10.1016/j.bpsc.2019.11.004. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020. PMID: 31918889 Free PMC article. No abstract available.

Abstract

Background: We used positron emission tomography imaging with [11C]raclopride to examine the effects of consumption of alcohol or placebo beverage by participants with alcohol use disorder (AUD) compared with healthy participants with and without family history of AUD. We sought to assess dopamine release following alcohol exposure in relation to AUD risk.

Methods: Three groups were enrolled: participants with AUD (n = 15) and healthy participants with family history negative (n = 34) or positive (n = 16) for AUD. Participants consumed a placebo (n = 65) or alcohol (n = 63) beverage in counterbalanced order before positron emission tomography scanning (128 scans). Binding potential (BPND) in the two drink conditions and the percent change in BPND between conditions were evaluated across striatal subregions. Subjective effects of beverage consumption were rated. Effects of group, drink order, and sex were evaluated.

Results: Alcohol resulted in greater dopamine release than did placebo in the ventral striatum (p < .001). There were no main effects of group, drink order, or sex on ventral striatum BPND or percent change in BPND. However, there was a drink order-by-group interaction (p = .02) whereby family history-positive participants who received placebo first had both lower placebo BPND and less difference between placebo and alcohol BPND than all other groups, consistent with expectation of alcohol powerfully evoking dopamine release in this group. Subjective responses showed the same order-by-group interaction.

Conclusions: Hyper-responsivity of the dopaminergic system in family history-positive participants to expectation of alcohol may contribute to the expression of familial risk for AUD.

Keywords: Alcohol use disorder; Dopamine; Familial risk; PET; Ventral striatum; [(11)C]raclopride.

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Figures

Figure 1.
Figure 1.
Alcohol-induced change in ventral striatal D2/3 receptor binding (ventral striatum [VST] percent change in binding potential [ΔBPND], the percent decrease from placebo day to alcohol day) by group and drink order. The family history–positive (FHP) group showed an opposite response to the drink conditions compared with the family history–negative (FHN) and alcohol use disorder (AUD) groups (p = .02, group-by-order interaction). Plot symbols indicate group mean and error bars indicate SEM. Participant group sizes were FHP: n = 8 alcohol beverage at first scan (AP) and n = 8 alcohol beverage at second scan (PA); FHN: n = 15 AP and n = 17 PA; AUD: n = 8 AP and n = 7 PA (data shown in Supplemental Table S3).
Figure 2.
Figure 2.
(A) [11C]Raclopride binding potential (BPND) for each group and drink order. Each group (family history–positive [FHP], family history–negative [FHN], alcohol use disorder [AUD]) is represented by four bars: the placebo day (Pl) and the alcohol day (Alc) for each order (alcohol beverage at first scan [AP]; alcohol beverage at second scan [PA]). In all three groups, alcohol (second bar in each pair) resulted in greater dopamine release (reduction in BPND) than placebo did. However, the FHP participants showed much smaller alcohol-induced reduction in BPND when placebo was first (FHP-PA) than when placebo was second (FHP-AP). In contrast, the FHN and AUD participants showed moderate BPND reductions between placebo and alcohol day that were similar regardless of drink order. The six within-group differences between the placebo and alcohol day for each order (as percent of placebo) are the six data points in Figure 1. Bar heights indicate group mean BPND and error bars indicate SD (data shown in Table 3). (B) [11C]Raclopride BPND for each group and drink order, voxelwise maps. These images display the BPND values shown as regional means in panel (A). Note that the greatest intensity changes from placebo to alcohol scan occur for the FHP-AP group, and the smallest changes occur for the FHP-PA group. MRI, magnetic resonance imaging; VST, ventral striatum.
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References

    1. Fibiger HC (1978): Drugs and reinforcement mechanisms: A critical review of the catecholamine theory. Annu Rev Pharmacol Toxicol 18:37–56. - PubMed
    1. Samson HH, Tolliver GA, Haraguchi M, Hodge CW (1992): Alcohol self-administration: Role of mesolimbic dopamine. Ann N Y Acad Sci 654:242–253. - PubMed
    1. Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, et al. (2003): Alcohol promotes dopamine release in the human nucleus accumbens. Synapse 49:226–231. - PubMed
    1. Yoder KK, Constantinescu CC, Kareken DA, Normandin MD, Cheng TE, O’Connor SJ, et al. (2007): Heterogeneous effects of alcohol on dopamine release in the striatum: A PET study. Alcohol Clin Exp Res 31:965–973. - PubMed
    1. Yoder KK, Morris ED, Constantinescu CC, Cheng TE, Normandin MD, O’Connor SJ, et al. (2009): When what you see isn’t what you get: Alcohol cues, alcohol administration, prediction error, and human striatal dopamine. Alcohol Clin Exp Res 33:139–149. - PMC - PubMed

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