Serotonin 1B receptor imaging in alcohol dependence

Objectives Although multiple components of serotonin (5-HT) systems have been implicated in alcohol dependence (AD), the 5-HT_1B receptor (5-HT_1BR) receives particularly strong support. We studied 5-HT_1BR binding potential (BP_ND) in 4 medication-free, recently abstinent (at least 4 weeks) patients with AD (1 female, age 33.5±10.2) compared to 5 matched healthy control subjects (HC) (1 female, age 32.4±8.7).

Methods [¹¹C]P943, a selective 5-HT_1BR antagonist tracer was synthesized using GE's FXC module and/or Bioscan's AutoLoop by methylation with C-11 methyl triflate or C-11 methyl iodide, respectively. Following a transmission scan, [¹¹C]P943 was injected by pump over one min. and HRRT list mode data were acquired for 120 min. Imaging data were analyzed using a multilinear reference tissue model (MRTM2).

Results We found reductions in limbic-cortical 5-HT_1B receptor BP_ND values in AD versus HC and elevated ventral striatal 5-HT_1B receptor BP_ND values (2.21±.57 versus 1.57±.32, p=.03) in AD versus HC. No influence of age, sex, BMI or amount of injected radiotracer was observed.

Conclusions The current data provide the first direct evidence that 5-HT_1B receptors are implicated in AD. The group differences in ligand binding are limited to circuits that were previously implicated in AD by human functional neuroimaging studies. Increased expression of ventral striatal 5-HT_1B receptors has been linked to AD in preclinical studies, a model that is supported by our pilot data.

Research Support This study was supported in part by grant RAA017540A.