Abstract
Oxytocin (OT), a hormone synthesized within the paraventricular nucleus and supraoptic nucleus of the hypothalamus, when given intracerebroventricularly, induces strong scratching behaviors. However, it is not clear whether intradermal injection (ID) of OT elicits itch sensation. Herein, we found that OT (0.02 mg/ml) did not elicit an itch-scratching response in mice but aggravated chloroquine (CQ, 3 mmol/L)-elicited scratching behavior. Similar to OT, arginine vasopressin (AVP, 0.02 mg/ml), which is structurally related to OT, also enhanced CQ-induced scratching behavior but did not directly induce scratching behavior in mice. Mechanistically, OT-mediated enhancement of CQ-induced scratching behavior was significantly suppressed by conivaptan (0.05 mg/ml), a vasopressin-1a receptor (V1AR) antagonist and 1,400 W (3 mg/kg), inhibitor of inducible nitric oxide synthase (iNOS), but not OT receptor (OTR) antagonist L-368,899 (0.05 mg/ml). Notably, conivaptan also directly decreased CQ-induced scratching. In conclusion, OT plays a role in CQ-induced scratching behavior via V1AR binding events. V1AR antagonists could be used as possible treatments for CQ-induced itch.
Highlights
Oxytocin (OT) is a peptide hormone produced by the paraventricular nucleus and supraoptic nucleus of the hypothalamus
OT, histamine, arginine vasopressin (AVP), conivaptan, and L-368,899 were bought from MCE (Monmouth Junction, New Jersey, USA).The inducible nitric oxide synthase blocker 1,400 W was obtained from APExBIO (Houston, TX, USA)
ID of OT (0.4 μg/site) alone did not generate significant enhancement in the scratching behavior compared with normal saline (NS) (P > 0.05).These results reveal that OT does not directly contribute to scratching behavior in mice (Figure 1, (Supplemental Video 1, OT only)
Summary
Oxytocin (OT) is a peptide hormone produced by the paraventricular nucleus and supraoptic nucleus of the hypothalamus. Because of social and sexual behavior regulatory functions in mammals, including humans, OT and Abbreviation: OT, oxytocin; CNS, central nervous system; AVP, arginine vasopressin; ID, intradermal injection; CQ, chloroquine; iNOS, inducible nitric oxide synthase; DMSO, dimethyl sulfoxide; ELISA, enzyme-linked immunosorbent assay; Mrgprs, Mas-related G protein-coupled receptors; OTR, oxytocin receptor; V1AR, vasopressin-1a receptor; PLCβ, phospholipase Cβ; Ca2+]i, intracellular Ca2+; NO, nitric oxide; DRG, dorsal root ganglia. Similar to OT, central administration of AVP robustly stimulated stereotypical scratching and autogrooming in mice (Bielsky et al, 2004) It is not clear whether intradermal injection (ID) of OT or AVP elicits scratching behavior. Chloroquine (CQ), the antimalarial drug, induces itch in humans and scratching in mice (Green et al, 2006) via a histamine-independent pathway linked to activation of Mas-related G protein-coupled receptors (Mrgprs) (Liu et al, 2009).
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