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    Disrupting enkephalin in the dorsal raphe nucleus (DRN) affects motivated behaviors. Loss of DRN enkephalin (DRN Penk) amplifies pain and avoidance, while reducing pleasure and social interaction.

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    Area of Science:

    • Neuroscience
    • Behavioral Science
    • Molecular Biology

    Background:

    • The endogenous opioid system modulates motivation and affect.
    • The dorsal raphe nucleus (DRN) is a key brain region for behavioral control and opioid signaling.

    Purpose of the Study:

    • To investigate the role of enkephalin signaling within the DRN in motivated behaviors.
    • To explore the cellular distribution and functional impact of DRN enkephalin.

    Main Methods:

    • CRISPR-Cas9 technology was used to disrupt preproenkephalin (Penk) in the DRN of Penk-Cre mice.
    • Behavioral assays assessed mechanical sensitivity, odor avoidance, sucrose preference, and social interaction.
    • Hiplex in situ hybridization was employed to analyze gene expression patterns within the DRN.

    Main Results:

    • Knockdown of enkephalin in the DRN (DRN Penk) enhanced inflammation-induced mechanical sensitivity and odor avoidance.
    • Loss of DRN Penk reduced sucrose preference and engagement with novel social stimuli.
    • DRN Penk was found to be expressed on glutamatergic and GABAergic cells, but not serotonin cells, and subtype-specific knockdown did not fully replicate behavioral effects.

    Conclusions:

    • Enkephalin signaling in the DRN plays a critical role in regulating both aversive and appetitive motivated behaviors.
    • The cellular distribution of DRN enkephalin suggests a distinct neuronal population mediating these behaviors, separate from canonical DRN mechanisms.