Serotonin Transporters in Alcoholism
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Observational

Summary: 
      This study will compare serotonin transporter proteins in people with alcoholism and healthy
      volunteers to examine how these proteins may be related to the inability of people with
      alcoholism to appropriately regulate their alcohol consumption. Serotonin transporters
      regulate levels of the brain chemical serotonin. Problems in this regulation have been
      implicated in alcoholism.

      Healthy normal volunteers and people who suffer from alcoholism who are between 18 and 75
      years of age may be eligible for this study. Candidates are screened with a medical history
      and physical examination, psychiatric diagnostic interview, blood and urine tests, an
      electrocardiogram, urine toxicology screen, and written psychological evaluations.

      Participants undergo positron emission tomography (PET) and magnetic resonance imaging (MRI)
      scanning to measure serotonin transporter levels in the brain.

      PET uses small amounts of a radioactive chemical called a tracer that "labels" the serotonin
      transporters in the brain. The tracer used in this study is [11C]DASB. For the procedure, the
      subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed
      to help keep the subject's head still during the scan so the images will be clear. A brief
      scan is done just before the radioactive tracer is injected. This scan provides measures of
      the brain that will help in the precise calculation of information from subsequent scans.
      After the tracer is injected through a catheter (plastic tube) placed in the arm, pictures
      are taken for about 2 hours.

      MRI uses a magnetic field and radio waves to produce pictures of brain structure. The subject
      lies on a bed that slides into the tube-like scanner, wearing earplugs to muffle loud noises
      the machine makes when the magnetic fields are switched. The scan takes about an hour, during
      which time the subject can communicate with the technician.
    

Detailed description: 
      Alcoholism is characterized by the inability of individuals to regulate their consumption of
      alcohol appropriately. Serotonergic dysfunction has been implicated in the pathophysiology of
      this illness. Serotonin transporters (SERT) critically regulate the tone of serotonergic
      transmission (Gobbi et al 2001). In a brain imaging study using the SPECT radioligand, [123I]
      Beta-CIT, male alcoholics who had abstained from alcohol for more than four weeks, had
      significantly reduced serotonin transporters in the raphe area of the brainstem compared to
      healthy control subjects (Heinz et al 1998). However, the [123I] Beta-CIT ligand, binds with
      high affinity to both the dopamine transporter (DAT) and SERT. Binding of [123I] Beta-CIT in
      regions rich in SERT or DAT have been attributed to SERT and DAT respectively but in regions
      of mixed innervation (e.g. cortical regions), it is not possible to distinguish between SERT
      and DAT.

      [11C]DASB is a PET ligand with high affinity for SERT with almost 1,000 fold selectivity
      versus DAT. Using this tracer, we will be able to measure SERT binding in cortical and
      subcortical brain regions including those with mixed innervation. [11C] DASB PET studies in
      humans (Houle et al 2000; Meyer et al 2001) indicate the feasibility of quantifying SERT
      binding in SERT rich regions. In the current protocol, we plan to use PET imaging with the
      radioligand, [11C] DASB, for serotonin transporter (SERT) to delineate regional abnormalities
      in SERT binding in two subject groups consisting of 30 patients with alcoholism and 30
      healthy volunteers. Our goal of the present study is to further our understanding of the
      roles of the serotonergic systems in the pathophysiology of alcoholism.
    

Keywords: 5 HT; Neuroreceptors; Radiotracer; Neuroimaging; Serotonin Transporter; Alcoholism; PET; Healthy Volunteer; HV