Positron Emission Tomography Imaging of the Serotonin Transporter and 5-HT_1A Receptor in Alcohol Dependence

Background: Rodent models as well as studies in humans have suggested alterations in serotonin (5-HT) innervation and transmission in early-onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5-HT transporter levels and 5-HT_1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre- and postsynaptic serotonergic transmission in the same alcoholic subjects and the first study of 5-HT_1A receptors in alcoholism. Methods: Fourteen alcohol-dependent subjects were scanned (11 with both tracers, 1 with [¹¹C]DASB only, and two with [¹¹C]WAY100635 only). Twelve healthy control subjects (HC) subjects were scanned with [¹¹C]DASB, and another 13 were scanned with [¹¹C]WAY100635. Binding potential (BP_p, mL/cm³) and the specific to nonspecific partition coefficient (BP_ND, unitless) were derived for both tracers using a two-tissue compartment model and compared with control subjects across different brain regions. Relationships to severity of alcoholism were assessed. Results: No significant differences were observed in regional BP_p or BP_ND between patients and control subjects in any of the regions examined. No significant relationships were observed between regional 5-HT transporter availability, 5-HT_1A availability, and disease severity, with the exception of a significant negative correlation between 5-HT transporters and years of dependence in amygdala and insula. Conclusion: This study did not find alterations in measures of 5-HT_1A or 5-HT transporter levels in patients with type II alcoholism.