Adaptive Control of Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents Persistent Hypophagia following Stress

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Jean, Alexandra | Laurent, Laetitia | Delaunay, Sabira | Doly, Stéphane | Dusticier, Nicole | Linden, David | Neve, Rachael | Maroteaux, Luc | Nieoullon, André | Compan, Valerie

Edité par CCSD ; Elsevier Inc -

International audience. Transient reduced food intake (hypophagia) following high stress could have beneficial effects on longevity, but paradoxically, hypophagia can persist and become anorexia-like behavior. The neural underpinnings of stress-induced hypophagia and the mechanisms by which the brain prevents the transition from transient to persistent hypophagia remain undetermined. In this study, we report the involvement of a network governing goal-directed behavior (decision). This network consists of the ascending serotonergic inputs from the dorsal raphe nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult restoration of serotonin 4 receptor (5-HT4R) expression in the mPFC rescues hypophagia and specific molecular changes related to depression resistance in the DR (5-HT release elevation, 5-HT1A receptor, and 5-HT transporter reductions) of stressed 5-HT4R knockout mice. The adult mPFC-5-HT4R knockdown mimics the null phenotypes. When mPFC-5-HT4Rs are overexpressed and DR-5-HT1ARs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia.

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