Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD). In animals, voluntary alcohol consumption increases DRD3 expression, and pharmacological blockade of DRD3s attenuates alcohol self-administration and reinstatement of alcohol seeking. However, these findings have yet to be translated in humans. This study used positron emission tomography (PET) and [¹¹C]-(+)-PHNO to compare receptor levels in several dopamine D2 receptor (DRD2) and DRD3 regions of interest between AUD subjects in early abstinence (n = 17; 6.59 ± 4.14 days of abstinence) and healthy controls (n = 18). We recruited non-treatment seeking subjects meeting DSM-5 criteria for AUD. We examined the relationship between DRD2/3 levels and both alcohol craving and alcohol motivation/wanting, using a cue reactivity procedure and an intravenous alcohol self-administration (IVASA) paradigm, respectively. [¹¹C]-(+)-PHNO binding levels in AUD subjects were significantly lower than binding in HCs when looking at all DRD2/3 ROIs jointly (Wilk’s Λ = .58, F(6,28) =3.33, p = 0.013, η²_p = 0.42), however there were no region-specific differences. Binding values demonstrate −12.3% and −16.1% lower [¹¹C]-(+)-PHNO binding in the SMST and SN respectively, though these differences did not withstand Bonferroni corrections. There was a positive association between [¹¹C]-(+)-PHNO binding in the SN (almost exclusively reflective of DRD3) and alpha (lower values reflect higher alcohol demand) in the APT after Bonferroni corrections (r = 0.66, p = 0.0080). This demonstrates that AUD subjects with lower DRD3 levels in the SN exhibit increased demand for alcohol. These results replicate previous findings demonstrating reduced DRD2/3 levels while also supporting a lack of DRD3 upregulation and potential downregulation in early abstinent AUD. Furthermore, the finding that binding in the SN is associated with alcohol demand warrants further examination.

临床前研究支持多巴胺 D3 受体 (DRD3s) 在酒精使用障碍 (AUD) 中的重要作用。在动物中，自愿饮酒会增加 DRD3 的表达，而 DRD3 的药理学阻断会减弱酒精的自我管理和恢复酒精寻求。然而，这些发现尚未在人类身上转化。本研究使用正电子发射断层扫描 (PET) 和 [ ¹¹ C]-(+)-PHNO 来比较 AUD 受试者早期戒断期间几个多巴胺 D2 受体 (DRD2) 和 DRD3 感兴趣区域的受体水平 ( n  = 17; 6.59 ± 4.14 天禁欲）和健康对照（n = 18)。我们招募了符合 AUD DSM-5 标准的非治疗寻求对象。我们分别使用提示反应程序和静脉内酒精自我给药 (IVASA) 范式检查了 DRD2/3 水平与酒精渴望和酒精动机/想要之间的关系。[ ¹¹ C]-(+)-PHNO 在 AUD 受试者中的结合水平显着低于 HC 中的结合水平，当同时查看所有 DRD2/3 ROI 时（Wilk's Λ = .58，F (6,28) =3.33，p  = 0.013 , η ² _p  = 0.42)，但是没有特定区域的差异。结合值显示低 -12.3% 和 -16.1% [ ¹¹C]-(+)-PHNO 分别在 SMST 和 SN 中结合，尽管这些差异不能承受 Bonferroni 校正。^{在 Bonferroni 校正后，SN 中的 [ 11} C]-(+)-PHNO 结合（几乎完全反映 DRD3）和 APT 中的 α（较低的值反映较高的酒精需求）之间存在正相关关系（ r  = 0.66，p  = 0.0080)。这表明 SN 中 DRD3 水平较低的 AUD 受试者表现出对酒精的需求增加。这些结果重复了先前的发现，证明 DRD2/3 水平降低，同时也支持早期戒断 AUD 中缺乏 DRD3 上调和潜在下调。此外，SN 中的结合与酒精需求相关的发现值得进一步研究。