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

Abstract

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 V1A 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 V1A 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 -1 mg kg 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 (100 mg·kg −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 V1A receptor rather than the OT receptor. Additionally, WAY 267,464 is not a simple OT receptor agonist, as it has functionally relevant V1A antagonist actions.

Cardioacceleration in alloparents in response to stimuli from prairie vole pups: The significance of thermoregulation

“…However, the effects of these peptides on cardioacceleratory and thermoregulatory aspects of prairie vole alloparental care are not well understood. Peripheral oxytocin administration leads to a decrease in heart rate and core body temperature in rats [39] -results which we have confirmed in the prairie vole (unpublished observations). In our earlier studies of prairie vole alloparenting, pup exposure was associated with increased activity in oxytocin neurons and a transient increase in peripheral oxytocin levels [6]; however, heart rate also increases [5].…”

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

“…In rats, chronic subcutaneous or ICV injections reduced blood pressure without impacting heart rate [177]. In contrast, acute administration of OT into the CNS or periphery is associated with increases, decreases, or no changes in heart rate [71,210,221,222], blood pressure [177,210,223], and body temperature [71,221] in mice or rats (for review see [224,225]). Preliminary data in our laboratory indicate that subcutaneous administration of OT does not significantly alter heart rate, blood pressure or body temperature at 90-min post-treatment in a limited number of sedated nonhuman primates (unpublished observations).…”

Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists

“…To examine the possibility whether the effect of MTII on body temperature involves A1 or AVP V1a receptors, we concurrently administered MTII with A1 receptor antagonist CPT at the dose of 1mg/kg or AVP V1a receptor antagonist SR at the dose of 1mg/kg. Both doses were described previously to sufficiently block A1 and AVP V1a receptors for body temperature regulation [19, 20]. Interestingly, while CPT produced no discernable effects on the effect of MTT on body temperature reduction (Fig.…”

“…Activation of A1 receptors and AVP V1a receptors caused rapid body temperature reduction [19, 20]. To examine the possibility whether the effect of MTII on body temperature involves A1 or AVP V1a receptors, we concurrently administered MTII with A1 receptor antagonist CPT at the dose of 1mg/kg or AVP V1a receptor antagonist SR at the dose of 1mg/kg.…”