• Scientists hunt for neurons responsible

    From ScienceDaily@1:317/3 to All on Tuesday, March 22, 2022 22:30:44
    Scientists hunt for neurons responsible for alcohol withdrawal
    Suspected amygdala neurons may not be to blame after all, new mouse study shows

    Date:
    March 22, 2022
    Source:
    Scripps Research Institute
    Summary:
    When a heavy alcohol drinker tries to take a night off, their
    body protests, with shaky hands, heart palpitations, anxiety
    and headaches.

    These acute symptoms of alcohol withdrawal -- but even more so
    the enduring emotional distress that lingers into protracted
    abstinence - - are one reason people with alcohol use disorders
    have a hard time quitting. Now, scientists have made new headway
    in understanding the basis of alcohol withdrawal in the brain.



    FULL STORY ==========================================================================
    When a heavy alcohol drinker tries to take a night off, their
    body protests, with shaky hands, heart palpitations, anxiety and
    headaches. These acute symptoms of alcohol withdrawal -- but even more so
    the enduring emotional distress that lingers into protracted abstinence
    -- are one reason people with alcohol use disorders have a hard time
    quitting. Now, scientists at Scripps Research have made new headway in understanding the basis of alcohol withdrawal in the brain.


    ========================================================================== Previously, a signaling molecule called corticotropin-releasing factor
    (CRF) was linked to alcohol withdrawal; when researchers block CRF in rats
    or mice addicted to alcohol, the animals drink less. Scientists believed
    that the suspect CRF is produced by neurons in a brain area called the
    central nucleus of the amygdala. But in the new study, published in
    the journal Molecular Psychiatry in March 2022, the team found that --
    at least in mice -- these cells aren't required for alcohol withdrawal
    or alcohol dependence.

    "Understanding the basis of withdrawal is incredibly important for
    treating alcohol addiction in humans, because this is one of the
    motivational drivers of excessive alcohol drinking," says Candice Contet,
    PhD, associate professor in the Department of Molecular Medicine at
    Scripps Research. "These findings weren't what we expected, but help
    us get closer to understanding alcohol addiction and the role of CRF."
    Many studies have established that CRF levels increase in the central
    nucleus of the amygdala of rats and mice during alcohol withdrawal as well
    as in response to other psychological stressors. Pharmaceutical companies
    are actively investigating how to target CRF signaling to treat a variety
    of psychological diseases including alcohol addiction. But results in
    humans have been inconclusive, and scientists have not been able to pin
    down which cells in the brain release CRF during alcohol withdrawal.

    Contet's group wanted to test the hypothesis that cells in the central
    amygdala produce the CRF necessary for alcohol withdrawal. In the new
    study, the researchers activated and blocked these amygdala-residing
    neurons in mice dependent on alcohol. First, they activated the neurons
    in various patterns designed to replicate cycles of repetitive drinking
    and withdrawal. However, activating these CRF-producing neurons had no
    effect on the drinking behavior of the mice, even though other experiments confirmed that CRF was getting released in the central amygdala. Next,
    the team showed that blocking these neurons also had no effect on the
    behavior of mice with alcohol dependence, which was surprising because
    it meant that the CRF known to signal in the amygdala to promote alcohol drinking wasn't being produced in that area.

    "We basically saw that activating these neurons within the central
    amygdala is not sufficient nor necessary for the escalation of drinking
    in mice," says Contet. "So it means that the CRF is coming to the central amygdala from somewhere else in the brain." Other neurons in the brain
    are known to produce CRF, but the team doesn't yet know which might be
    involved in alcohol dependence.

    "These findings were surprising but highlight the complexity of the CRF
    system and the changes in brain circuitry that occur following chronic
    alcohol exposure," says Melissa Herman, a former Scripps Research
    postdoctoral research associate and co-first author of the new paper.

    When the team looked at the spatial patterns of organization of the
    amygdala neurons they were studying, they made another unexpected
    observation -- the CRF neurons weren't organized the same way in mice
    brains as they are in rat brains. The observation, Contet says, suggests
    that there might be some variation in CRF between species. This also
    could explain why the amygdala neurons in question have been found to be necessary for alcohol withdrawal in rats but, according to the new data,
    not in mice.

    "Our data has to be taken with a grain of salt when it comes to
    implications for humans," she says. "Since there's this important
    difference between rats and mice, more work is definitely needed to
    figure out the relevance to humans." The group is planning experiments
    to further understand the differences in CRF between rats and mice,
    as well as pin down which other neurons in the brain might be involved
    in its production during alcohol withdrawal.

    This work was supported by funding from the National Institutes of Health (AA024198, AA026685, AA027636, AA027372, AA006420, AA021491, AA015566,
    AA02300, and AA024952).


    ========================================================================== Story Source: Materials provided by Scripps_Research_Institute. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Max Kreifeldt, Melissa A. Herman, Harpreet Sidhu, Agbonlahor
    Okhuarobo,
    Giovana C. Macedo, Roxana Shahryari, Pauravi J. Gandhi, Marisa
    Roberto, Candice Contet. Central amygdala corticotropin-releasing
    factor neurons promote hyponeophagia but do not control alcohol
    drinking in mice.

    Molecular Psychiatry, 2022; DOI: 10.1038/s41380-022-01496-9 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220322141128.htm

    --- up 3 weeks, 1 day, 10 hours, 51 minutes
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)