title: 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: OBJECTIVE
  There 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.
  
  
  METHODS
  Biotelemetry in freely moving male Wistar rats was used to examine body temperature and heart rate after OT (0.01 - 1 mg kg(-1); i.p.), AVP (0.001 - 0.1 mg kg(-1); i.p.) or WAY 267,464 (10 and 100 mg kg(-1); i.p.). The actions of the OT receptor antagonist Compound 25 (C25, 5 and 10 mg kg(-1)) and V1A receptor antagonist SR49059 (1 and 10 mg kg(-1)) were studied, as well as possible V1A receptor antagonist effects of WAY 267,464.
  
  
  RESULTS
  OT 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
  Peripherally 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.
authors.affiliation: School of Psychology, University of Sydney, Sydney, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Hicks
authors.forename: L
authors.initials: L
authors.lastname: Ramos
authors.forename: T
authors.initials: T
authors.lastname: Reekie
authors.forename: G H
authors.initials: GH
authors.lastname: Misagh
authors.forename: R
authors.initials: R
authors.lastname: Narlawar
authors.forename: M
authors.initials: M
authors.lastname: Kassiou
authors.forename: I S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors / Q000502:physiology; D017483:Receptors, Vasopressin / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology*
chemical_list: C547280:4-(3,5-dihydroxybenzyl)-N-(2-methyl-4-((1-methyl-4,10-dihydropyrazolo(3,4-b)(1,5)benzodiazepin-5(1H)-yl)carbonyl)benzyl)piperazine-1-carboxamide; D065092:Antidiuretic Hormone Receptor Antagonists; D006727:Hormone Antagonists; D007211:Indoles; D011720:Pyrazoles; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001569:Benzodiazepines; D010121:Oxytocin; C082134:relcovaptan
keywords: Compound 25; SR49059; WAY 267,464; biotelemetry; body temperature; heart rate; oxytocin; vasopressin; vasopressin V1A receptor