Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats

Background and PurposeThere is current interest in oxytocin (OT) as a possible therapeutic in psychiatric disorders. However, the usefulness of OT may be constrained by peripheral autonomic effects, which may involve an action at both OT and vasopressin V-1A receptors. Here, we characterized the cardiovascular and thermoregulatory effects of OT, vasopressin (AVP) and the non-peptide OT receptor agonist WAY 267,464 in rats, and assessed the relative involvement of the OT and V-1A receptors in these effects. Experimental ApproachBiotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 - 1mg kg(-1); i.p.), AVP (0.001 - 0.1mg kg(-1); i.p.) or WAY 267,464 (10 and 100mg kg(-1); i.p.). The actions of the OT receptor antagonist Compound 25 (C25, 5 and 10mg kg(-1)) and V-1A receptor antagonist SR49059 (1 and 10mg kg(-1)) were studied, as well as possible V-1A receptor antagonist effects of WAY 267,464. Key ResultsOT and AVP dose-dependently reduced body temperature and heart rate. WAY 267,464 had similar, but more modest, effects. SR49059, but not C25, prevented the hypothermia and bradycardia induced by OT and AVP. WAY 267,464 (100mgkg(-1)) prevented the effects of OT, and to some extent AVP. Conclusions and ImplicationsPeripherally administered OT and AVP have profound cardiovascular and thermoregulatory effects that appear to principally involve the V-1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V-1A antagonist actions.