Acute Hypernatremia Exerts an Inhibitory Oxytocinergic Tone That Is Associated With Anxiolytic Mood in Male Rats

Anxiety disorders are the most common psychiatric illnesses and are associated with heightened stress responsiveness. The neuropeptide oxytocin (OT) has garnered significant attention for its potential as a treatment for anxiety disorders; however, the mechanism mediating its effects on stress responses and anxiety is not well understood. Here we used acute hypernatremia, a stimulus that elevates brain levels of OT, to discern the central oxytocinergic pathways mediating stress responsiveness and anxiety-like behavior. Rats were rendered hypernatremic by acute administration of 2.0 M NaCl and had increased plasma sodium concentration, plasma osmolality, and Fos induction in OT-containing neurons relative to 0.15 M NaCl-treated controls. Acute hypernatremia decreased restraint-induced elevations in corticosterone and created an inhibitory oxytocinergic tone on parvocellular neurosecretory neurons within the paraventricular nucleus of the hypothalamus. In contrast, evaluation of Fos immunohistochemistry det...