INIA: Stress, Anxiety of Alcohol Abuse

    Project: Research project

    Description

    DESCRIPTION (provided by applicant):
    The Administrative Core Component will make sure that all aspects of the INIA
    consortium work at an optimal level. The core will serve as an identifiable
    center for entire INIA consortium. This core will be responsible for decisions
    about research directions, including review of component progress and
    inclusion and exclusion of investigators. The core will also ensure the proper
    flow of information between the different consortium components, and flow of
    information to the larger research community in collaboration with the
    Bioinformatics Core. The duties of this core will also include organizing and
    financing all INIA committee meetings, retreats and research presentations.
    The administrative core will also track the INIA consortium finances and
    assist in budget planning for the different research components and cores.
    Stress contributes to excessive drinking and alcoholism, but the molecular and
    cellular mechanisms that underlie alcohol-stress interactions are not well
    understood. The brain circuitry involved in coordinating and producing
    responses to stress is known, and includes the extended amygdala (amygdala,
    bed nucleus of the stria terminalis and nucleus accumbens (NAc)], the
    hippocampus (HPC), the prefrontal cortex (PFC) and the hypothalamus. There is
    also considerable evidence implicating the neurotransmitters glutamate, GABA
    and serotonin (5-HT) in stress-induced neurophysiological responses in these
    brain regions. Alcohol effects on synaptic transmission in stress-related
    brain regions have not been characterized in much detail. Furthermore the role
    of the aforementioned neurotransmitters in these responses has not been
    examined. INIA component I will focus on examining synaptic transmission in
    amygdala, HPC, NAc and PFC in wild-type mice and mice with gene-targeted
    knockouts of the GABAAbeta3. Delta and gamma2 subunits, the NMDAR2A subunit,
    theGluRA subunit, the5-HTIA receptor and SERT. Similar experiments will be
    performed in selected randomly mutagenized mice identified in INIA component
    3, and mice from selected BxD recombinant strains identified in INIA component
    4. Brain slice preparations and isolated neurons will be examined from all of
    these groups of mice following chronic alcohol exposure and withdrawal.
    chronic alcohol self-administration and stress-induced reinstatement of
    alcohol drinking. Excitatory and inhibitory synaptic transmission will be
    measured using field potential and intracellular recording in brain slices
    containing the regions of interest. Synaptic plasticity will also be examined
    in brain slices. Acutely isolated neurons will be used to examine changes in
    neurotransmitter receptor function, and single-cell MRNA profiling will be
    used to identify neuronal subtypes. Serotonin release and reuptake will be
    examined in brain slices and synaptosomal preparations from the brain regions
    of interest. These studies will provide crucial information about
    neuroadaptive changes in synaptic transmission and plasticity induced by ETOH
    and stress in brain regions implicated in stress responses. We will also
    gather information about the role of particular neurotransmitter receptors and
    transporters in these neuroadaptive changes. Findings from this project " Ill
    be compared to data gathered in INIA components 2, 3 and 4 to generate more
    integrated information about the neuroadaptive changes related to
    alcohol-stress interactions. In future studies we will use mice developed by
    the Knockout Mouse Core and in component 7 in studies such as those proposed
    at present. Information gained in this component will be compared with that
    gained in the primate studies proposed in component 5, and will be shared with
    the larger research community on the INIA web page with the help of the
    Bioinformatics Core. It is predicted that information from this project will
    contribute to a better under- standing of the mechanisms underlying
    stress-alcohol interactions that may lead to better therapies for treating
    excessive drinking and alcoholism.
    StatusFinished
    Effective start/end date2/1/021/31/17

    Funding

    • National Institutes of Health: $504,793.00
    • National Institutes of Health: $547,406.00
    • National Institutes of Health: $486,709.00
    • National Institutes of Health: $547,406.00
    • National Institutes of Health: $669,750.00
    • National Institutes of Health: $483,977.00
    • National Institutes of Health: $202,879.00
    • National Institutes of Health: $650,102.00
    • National Institutes of Health: $530,984.00
    • National Institutes of Health: $682,792.00
    • National Institutes of Health: $672,803.00
    • National Institutes of Health: $636,064.00
    • National Institutes of Health: $687,888.00
    • National Institutes of Health: $677,483.00
    • National Institutes of Health: $788,558.00
    • National Institutes of Health: $620,029.00

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    Anxiety
    Alcoholism
    Drinking
    Alcohol Drinking
    Brain
    abuse
    alcohol
    advisory panel
    Ethanol
    anxiety
    Synaptic Transmission
    Alcohols
    Research
    pilot project
    management
    Serotonin
    Neuronal Plasticity
    research project
    Nucleus Accumbens
    Allostasis

    ASJC

    • Medicine(all)