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Keywords:

  • [18F]Fallypride;
  • addiction;
  • alcoholism;
  • detoxification;
  • dopamine D2/3 receptor;
  • PET

ABSTRACT

Positron emission tomography (PET) shows reduced binding of the dopamine D2/3 antagonist [11C]raclopride in striatum of withdrawn psychostimulant abusers, but not consistently in patients with alcohol dependence (AD). We make first use of the high affinity ligand [18F]fallypride to obtain serial measures of D2/3 receptor availability in striatal and extrastriatal regions of AD patients undergoing detoxification. Seventeen patients (mean age 44 ± 5y) with AD and 14 age-matched healthy volunteers participated. Each patient underwent [18F]fallypride PET upon hospital admission, and again 1–2 weeks later; two patients achieving abstinence, and two with substantial harm reduction had additional PET follow-up at 1 year. Dynamic 180-minute PET recordings were used for volume of interest (VOI)-based and voxel-wise analysis of [18F]fallypride binding potential (BPND). Mean baseline BPND in striatum of the AD patients (15.7 ± 3.6) was unaltered during short-term follow-up, and did not differ from that in healthy controls (16.8 ± 3.0); however, BPND was 10–20% lower in thalamus, hippocampus, and insular and temporal cortex of the AD patients (P < 0.05). Age-dependent declines in BPND were very small in controls, but more pronounced and widespread in the AD group. Striatal and thalamic BPND increased by 30% in four patients with long-term abstinence or reduced alcohol consumption. VOI-based [18F]fallypride PET analyses revealed group differences in D2/3 receptor availability primarily in extra-striatal regions. Age-related loss of dopamine D2/3 receptors was more pronounced in AD patients. Receptor availability was unaltered by acute withdrawal, but increased in the subgroup of patients with long-term follow-up, suggesting reversibility of receptor changes.