A symmetric systemic challenge elicits a right-biased response mediated by vasopressin signaling.

Bilaterian animals exhibit functional asymmetry-population-level, directional left-right differences in physiology and behavior, including responses to spatially symmetric environmental challenges. Whether such symmetry-to-asymmetry conversion can be driven at the systems level by neurohormonal regulators remains unclear. Here we tested whether a spatially symmetric neuroendocrine challenge-water deprivation (WD)-can elicit a directional left-right physiological response in rats using hindlimb postural asymmetry (HL-PA), a binary readout that quantifies left- versus right-sided hindlimb flexion. Twenty-four hours of WD induced robust HL-PA with right hindlimb flexion, revealed under anesthesia. The asymmetry persisted after complete thoracic spinal cord transection, suggesting that humoral signaling, rather than descending neural commands, maintains the postural bias. Dehydration activated the hypothalamic arginine vasopressin (AVP) system. Furthermore, a V1B antagonist (SSR-149415) and a V1A/V2 antagonist (conivaptan) abolished and partially attenuated WD-induced HL-PA, respectively, supporting an AVP-dependent mechanism that likely operates at least two anatomical sites. AVP signaling may involve pituitary V1B-dependent endocrine output and spinal V1A actions; consistent with the latter, expression of AVP V1A receptors is right-biased in lumbar spinal cord. Together, these findings identify WD as a symmetric systemic challenge capable of unmasking a directional peripheral bias and implicate vasopressin signaling in left-right physiological regulation. More broadly, they suggest that symmetric homeostatic challenges engage neuroendocrine mechanisms that shift the balance between left- and right-sided physiological functions.