The neurobiology of alcoholism in humans is still poorly understood. The general aim of this proposal is to test the hypothesis that alcoholism is associated with a deficits in serotonin function. Using neuroreceptor imaging and a state of the art positron emission tomography (PET) scanner, we propose to evaluate the association between alcoholism and alteration in pre-and post synaptic parameters of serotonin transmission in the midbrain and neocortical regions in: 1) 5-HT transporters density; 2) 5-HT1A receptors density. 5-HT transporters (specific aim #1) and 5-HT1A receptors density. Recently abstinent alcoholics (within 3 to 4 weeks of abstinence) and 25 healthy controls matched for age, gender, ethnicity, parental socioeconomic status and nicotine dependence. The hypotheses are that, compared to matched control subjects, alcoholics will display lower 5-HT transporter and 5-HT1A receptor density. These alterations will not be fully explainable by loss of gray matter (specific aim #3) as they will persist after correction for differences in gray matter volume between alcoholics and controls, using a combination of Magnetic Resonance Imaging (MRI) driven regions of interest analysis, gray/white matter segmentation and correction of partial voluming effects. Finally we will obtain acetyl-aspartate )NAA) measurements using Magnetic Resonance Spectroscopy (MRS) and correlate these measurements with MRI volume in ROIs (specific aim #4). This study will provide a comprehensive description of synaptic serotonin parameters in alcoholism. If indeed deficits in 5-HT function are found in chronic alcoholics, we can examine as a second step, possibly in the renewal of this application, whether these deficits represent a toxic effect of alcohol or a vulnerability factor. Understanding the neurochemical abnormalities underlying vulnerability to alcoholism would guide future treatment interventions and risk prevention strategies.
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