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

作者：Jean Alexandra; Laurent Laetitia; Delaunay Sabira; Doly Stephane; Dusticier Nicole; Linden David; Neve Rachael; Maroteaux Luc; Nieoullon Andre; Compan Valerie

来源：Cell Reports, 2017, 21(4): 901-909.

DOI：10.1016/j.celrep.2017.10.003

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-5HT(4)R knockdown mimics the null phenotypes. When mPFC-5-HT(4)Rs are overexpressed and DR-5HT(1A)Rs are blocked in the DR, hypophagia following stress persists, suggesting an antidepressant action of early anorexia.

• 出版日期2017-10-24