Dopaminergic dysfunction in substance-related and behavioral addictions: Evidence from SPECT imaging in alcohol and gambling disorders

Objectives: Dopamine plays a central role in mediating addictive disorders (ADs), encompassing both substance-related and behavioral conditions. Some neurobiological alterations reflect trait-like vulnerability, while others are state-dependent, arising from intoxication and withdrawal. In this study, we examined striatal dopamine transporter (DAT) availability in individuals with alcohol use disorder (AUD) and gambling disorders (GD) to disentangle core mechanisms underlying addiction. Methods: The study involved individuals with AUD (n = 14), GD (n = 14), and healthy controls (HC; n = 25). DAT binding in the bilateral caudate and putamen was assessed using single-photon emission computed tomography (SPECT) with the radiotracer 123I-FP-CIT. ADs participants underwent evaluation for addiction-specific and general psychopathological symptom severity. Results: In the caudate, individuals with AUD showed higher DAT availability compared to those with GD (d = 2.234) and HC (d = 1.368). No lateralization effects were observed in any of the models. Across all ADs, DAT availability in the left putamen was significantly associated with the duration of abstinence over the past four weeks (rho = 0.444), after covarying for depression and irrespective of the diagnostic group. Conclusions: Our findings support a DAT-mediated involvement in core neurobiological processes underlying both substance-related and behavioral addictions. We propose that, in ADs, a predisposing striatal DAT deficiency may coexist with alcohol-induced upregulations (substance-specific) and with dynamic, time-sensitive fluctuations related to withdrawal processes (non-specific, addiction-related). Although a small sample size limits the generalizability of this study, these results may stimulate further research toward developing targeted therapeutic interventions.