Involvement of the hypothalamus–raphe magnus–spinal defecation center axis in stress-induced defecation in rats

Acute psychological stress stimulates colonic motility; however, the specific descending neural pathways linking the brain to the distal colon remain incompletely characterized. Here, we provide evidence that the hypothalamus‒raphe magnus‒spinal cord‒pelvic nerve pathway mediates stress-induced defecation in male Sprague–Dawley rats. Using urethane-anesthetized rats, we used viral tracing, pharmacological, and chemogenetic approaches to show that hypothalamic neurons projecting to the raphe magnus nucleus activate descending serotonergic neurons probably via oxytocinergic signaling, thereby stimulating colorectal motility through the pelvic nerve. In conscious rats, inhibiting this pathway suppresses stress-induced defecation. These findings highlight the role of the hypothalamus‒raphe magnus‒spinal defecation center axis in transmitting acute psychological stress to the colorectum. The hypothalamic neurons projecting to the raphe magnus nucleus activate descending serotonergic neurons, thereby activating spinal defecation center. The pathway plays a role in transmitting acute psychological stress to the colorectum.