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    Home > Active Ingredient News > Study of Nervous System > Nature Neuroscience: The loop mechanism of pain-induced anhedonia

    Nature Neuroscience: The loop mechanism of pain-induced anhedonia

    • Last Update: 2021-11-15
    • Source: Internet
    • Author: User
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    The persistence of pain will cause emotional decision-making, reward evaluation and motivational behavior disorders, which will further develop into negative emotional states such as anxiety and depression
    .

    The common feature of these negative emotions is the decrease in starting or completing goal-oriented behaviors (lack of the ability to feel pleasure), which is called anhedonia
    .

    The neural circuit of the ventral tegmental area (VTA) dopaminergic neurons projecting to the nucleus accumbens (NAc) plays a key role in regulating reward behavior and motivational behavior
    .

    The imaging data showed that the release of dopamine and the activation of dopamine receptors in the nucleus accumbens brain area of ​​patients with pain were decreased
    .

    The activity of VTA dopaminergic neurons is mainly regulated by inhibitory synaptic input from the medial tegmental nucleus neurons (RMTg), NAc, ventral globus pallidus, and stria terminalis nucleus
    .

    On October 18, 2021, the Jose A.
    Morón research team of the University of Washington revealed the neural circuit mechanism of pain reducing target motivational behavior in rodents, which provides a new way for further research on the co-morbid mechanism of negative mood diseases such as pain and depression Clues
    .

    Fiber-optic calcium imaging technology records the calcium ion activity during the process of rewarding rats.
    Researchers have found through in vivo fiber-optic calcium imaging technology that in the pain model rats, the number of pressure rods is reduced, and the activity of VTA dopaminergic neurons is also significantly reduced.

    .

    In vitro electrophysiological experiments further found that VTA dopaminergic neurons in painful rats received more inhibitory effects from inhibitory neurons, which caused hyperpolarization and decreased intrinsic excitability
    .

    Activate VTA dopaminergic neuron activity Chronic activation of VTA dopaminergic neuron activity through chemical genetics technology can promote the reward motivation behavior of pain model rats
    .

    In addition, the injection of retrovirus carrying Cre recombinase virus into NAc brain area and the injection of Cre enzyme-dependent excitatory chemogenetic virus into VTA to achieve specific activation of the VTA-NAc neural circuit can also promote the motivational behavior of painful rats.
    : Willing to get more sugar water rewards
    .

    The researchers further tested whether the pain changes the reward behavior in the natural state by setting different gradients (5%, 30%, 60%) of sucrose solutions.
    They found that the consumption of 5% and 30% sucrose solutions in rats increased significantly, but in The consumption of these two concentrations of sucrose solution was reduced in painful rats
    .

    However, activating dopaminergic neurons in the VTA region can promote the consumption of 5% sucrose solution in painful mice, which indicates that pain can "shift right" the reward value of sucrose, and activating VTA dopamine neurons can eliminate this "right" reward value.
    Move"
    .

    Electrophysiological experiments show that RMTg brain regions can inhibit the activity of VTA dopamine neurons
    .

    After chronically activating inhibitory neurons in the RMTg brain area, rats consumed 5% sucrose solution, which is similar to the anhedonia state caused by pain
    .

    In order to further determine the role of inhibitory neurons in the RMTg brain region in pain-mediated anhedonia, after chronically inhibiting the inhibitory neurons in the RMTg brain region of pain rats, these rats showed a normal level of consumption of 5% sucrose solution.
    That is to reverse the anhedonia behavior caused by pain
    .

    In summary, this article found that pain enhances the inhibitory effect of RMTg brain area inhibitory neurons on VTA brain area dopaminergic neurons, and this inhibitory effect is the key neurobiological basis for anhedonia
    .

    [References] 1.
    https://doi.
    org/10.
    1038/s41593-021-00924-3 The pictures in the text are from the references
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