Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach

Abstract

Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine‐related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying 18F‐fallypride positron emission tomography (18F‐PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low‐risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future.

Association between DRD2/ANKK1 TaqIA allele status and striatal dopamine D2/3 receptor availability in alcohol use disorder

“…The results of this study demonstrate that DRD2/3 availability is reduced in the associative, sensorimotor, and limbic striatum of AUD patients compared to HCs. This supports our hypothesis and is in line with our previous finding of reduced striatal DRD2/3 availability in AUD patients compared to individuals at high risk of AUD and HCs (Gleich et al, 2020;Sebold et al, 2019). On the other hand, contrary to our hypothesis we did not find any association between DRD2/ANKK1 TaqIA allele status and striatal DRD2/3 availability, although this result must be interpreted with caution because of the limited effect size and relatively small sample size.…”

“…Despite the well-known contribution of dopaminergic impairment to AUD and other substance use disorders (Gleich et al, 2020;Heinz et al, 2005;Martinez et al, 2005;Volkow et al, 1996Volkow et al, , 2002Volkow et al, , 2007, few studies have examined the relationship between DRD2/3 and genetic predisposing factors in AUD, possibly because of power issues in PET studies, which may also have contributed to the null result in this study. Therefore, our findings are noteworthy as other studies might have experienced similar limitations.…”

“…To date there have been no in vivo studies investigating DR availability and DRD2/ANKK1 TaqIA allele status in AUD, except for a postmortem study reporting a link between the binding characteristics of DRD2 in the cerebral cortex and AUD (Noble et al, 1991). We previously showed that dorsostriatal DRD2/3 availability was reduced in AUD patients and individuals at high risk for developing AUD compared to HCs (Gleich et al, 2020).…”

“…Chronic alcohol intake is associated with lower dopamine receptor availability. In particular, reduced availability of dopamine D2 and D3 receptors (DRD2 and DRD3, respectively) in the striatum of patients with alcohol dependence compared to healthy controls (HCs) has been demonstrated by several positron emission tomography (PET) studies (Erritzoe et al, 2014;Gleich et al, 2020;Heinz et al, 2004Heinz et al, , 2005Hietala et al, 1994;Rominger et al, 2012;Volkow et al, 2002Volkow et al, , 2007 and described in recent reviews (Alexandre et al, 2019;Kamp et al, 2018). However, it is unclear whether these changes reflect neuroadaptations to excess acute striatal dopamine release during regular substance use or are the result of genetic predisposition for substance use disorder.…”

Differential brain responses to alcohol‐related and natural rewards are associated with alcohol use and problems: Evidence for reward dysregulation

“…92,93 and AUD severity. 94 Preclinical research offers complementary evidence in that dopamine D 2 receptor knock-out rats show increased incentive motivation for drugs, 95,96 and reduced dopamine D 2 receptor availability modulates alcohol preference 97 and is present in rats who attribute incentive value to reward-predictive cues (i.e., expressing the sign-tracking phenotype; see Flagel et al 98 and Tournier et al 99 ).…”