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Center for the Translational Neuroscience of Alcohol (CTNA)
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INFORMATION FOR

CTNA-1 Projects

  • Project 1: PI: Eric Nestler MD, PhD, TRANSCRIPTION FACTORS, GLUTAMATERGIC FUNCTION, ETHANOL REWARD, AND ADAPTATION TO CHRONIC ETHANOL
    Dr. Nestler has focused his work on a systematic mapping of ?FosB induction in brain by chronic alcohol administration, using several methods of alcohol exposure. He has characterized the specific cell types within these regions where this alcohol induction of ?FosB occurs, in the search for target genes for ?FosB, and hence for alcohol. The data indicate that alcohol-induced accumulation of ?FosB in nucleus accumbens, dorsal striatum, amygdale, and prefrontal cortex.
    Working in collaboration with George Koob (Scripps Research Institute) and Adron Harris (University of Texas at Austin), they found that ?FosB may reduce the effects of alcohol on balance, while enhancing the anxiolytic effects of alcohol.
  • Project 2: PI: Joel Gelernter MD, GUIDED FAMILY-CONTROLLED LINKAGE DISEQUILIBRIUM SCAN FOR ALCOHOL DEPENDENCE AND PFC-RELATED ENDOPHENOTYPES
    Dr. Gelernter performed SNP-based fine-mapping of regions of chromosome 1 and 11 that show linkage disequilibrium with alcohol dependence. He collaborated with other CTNA investigators to identify genetic association with EtOH-related endophenotypes.
  • Project 3: PI: Graeme Mason PhD, 13C MRS MEASUREMENT OF GLUTAMATE NEUROTRANSMITTER CYCLING IN INDIVIDUALS WITH FAMILIAL VULNERABILIUTY TO ALCOHOLISM, RECENTLY DETOXIFIED ALCOHOLICS, LONG-TERM SOBER ALOCHOLICS, AND HEALTHY INDIVIDUALS
    Dr. Mason developed 13C and 1H MRS GABA acquisition measurements in order to assess the rate of GABA synthesis in individual subjects.
  • Project 4: PI: Anissa Abi-Dargham MD, PRESYNAPTIC AND POSTSYNAPTIC 5-HT RECEPTOR ABNORMALITIES IN ALCOHOLISM: A PET STUDY
    Dr. Abi Dargham’s protocol focused on a comparison of serotonin transporter binding potential (BP) between alcohol dependent subjects and healthy controls. It combined [11C]WAY100635 and [11C]DASB, as a superior tracer for the serotonin transporter Alcohol dependent subjects were found to have a decrease in D2 receptor availability in the ventral and dorsal regions of the striatum compared to healthy controls and the reduction in striatal D2 receptors correlated with the daily intake of alcohol.
  • Project 5: PI: Ismene Petrakis MD, ALTERED NMDA RECEPTOR FUNCTION WITH FAMILIAL ALCOHOLISM RISK
    Dr. Petrakis found that people with a family history of alcoholism (FHP) have altered sensitivity to the behavioral effects of ethanol, and are at higher risk of developing alcoholism, relative to healthy individuals without a family history (FHN). She found that FHP individuals have an altered response to the NMDA antagonist, ketamine, compared to FHN individuals. This project was expanded for CTNA-2.
  • Project 6: PI: Suchitra Krishnan-Sarin PhD, DIFFERENTIAL INTERFERENCE WITH ETHANOL SELF-ADMINISTRATION BY NALTREXONE IN ALCOHOLIC INDIVIDUALS WITH OR WITHOUT FAMILIAL ALCOHOLISM
    This project utilized the laboratory paradigm for detecting the effects of opiate antagonists on alcohol drinking. Dr. Krishnan-Sarin found that the effect of naltrexone on drinking occurs primarily in FHP subjects. This project was expanded to include memantine as a treatment group for CTNA2.
  • Pilot 7: PI: William Corbin PhD, ACUTE EFFECTS OF ALCOHOL ON INFORMATION PROCESSING AND BEHAVIORAL CONTROL
    Dr. Corbin studied the effects of alcohol on inhibition of behavioral response, and the relation between behavioral inhibition and risk factors for alcohol-related problems. He found a trend toward alcohol impairment on sensitivity to the stimuli presented in the task (go and stop signals). This effect is apparent despite attempts among participants in the alcohol condition to slow themselves down to compensate for impairment.
  • Pilot 8: PI: Jane Taylor PhD, BEHAVIORAL AND MOLECULAR CONSEQUENCES OF CHRONIC ETHANOL ADMINISTRATION IN THE RAT.
    Dr. Taylor examined how molecular adaptations in the mesocorticolimbic structures contribute to neurocognitive effects of ethanol. Pilot work focused on spinophillin, the controller of protein phosphatase 1 (PP1) that is an antagonist of NMDA activity through inhibition of channel conductance. This project investigated how regulatory mechanisms affect incentive learning and cognitive/ibhibitory functions in alcoholism.
  • Pilot 9: PI: Julie Staley PhD, [123I]5-IA-85830 SPECT IMAGING OF ß2-NICOTINIC ACETYLCHOLINE RECEPTORS IN ALCOHOLISM
    Dr. Staley studied whether thalamic and cortico-limbic ß2 nicotine acetylcholine receptors (ß2~nAChR) are increased during sobriety in alcohol-dependent nonsmokers with a family history of alcoholism. She used SPECT imaging of ß ß2~nAChR to assess adaptations during the early development of sobriety.