Brain allopregnanolone induces marked scratching behaviour in diet-induced atopic dermatitis mouse model

Allopregnanolone (ALLO) is a neurosteroid produced in the brain, but so far, no study has explored its link with itching. Herein, we used a diet-induced atopic dermatitis mouse model to examine whether exogenously administered and endogenously produced ALLO contribute to inducing scratching. Systemic administration of ALLO elicited robust scratching in the atopic dermatitis model, while it did not affect spontaneous and pruritogen-induced scratching in normal mice. ALLO caused scratching when administered intracisternally, but not when administered intrathecally or intradermally, suggesting the involvement of supraspinal mechanisms. Pharmacological analyses suggested that both γ-aminobutyric acid type A receptor activation and serotonin type 3 receptor inhibition were involved in ALLO-induced scratching. We next examined whether endogenously produced ALLO is involved in ethanol-induced scratching in atopic dermatitis mice, because ethanol administration increases ALLO in rodent brain. Acute ethanol administration increased brain ALLO levels, which coincided with increased scratching. Pre-treatment with finasteride, a synthetic ALLO inhibitor, suppressed ethanol-induced scratching and ALLO production in the brain. Collectively, our results demonstrated for the first time that ALLO administration caused marked scratching in atopic dermatitis mice, and ethanol-induced scratching may be mediated through endogenously produced brain ALLO.