title: WAY 267,464, a non-peptide oxytocin receptor agonist, impairs social recognition memory in rats through a vasopressin 1A receptor antagonist action.
abstract: BACKGROUND
  Recent in vitro studies suggest that the oxytocin receptor (OTR) agonist WAY 267,464 has vasopressin 1A receptor (V1AR) antagonist effects. This might limit its therapeutic potential due to the positive involvement of the V1AR in social behavior.
  
  
  OBJECTIVE
  The objective of this study was to assess functional V1AR antagonist-like effects of WAY 267,464 in vivo using a test of social recognition memory.
  
  
  METHODS
  Adult experimental rats were tested for their recognition of a juvenile conspecific rat that they had briefly met 30 or 120 min previously. The modulatory effects of vasopressin (AVP), the selective V1AR antagonist SR49059, and WAY 267,464 were examined together with those of the selective OTR antagonist Compound 25 (C25). Drugs were administered immediately after the first meeting.
  
  
  RESULTS
  Control rats showed recognition of juveniles at a 30 min, but not a 120 min retention interval. AVP (0.005, but not 0.001 mg/kg intraperitoneal (i.p.)) improved memory such that recognition was evident after 120 min. This was prevented by pretreatment with SR49059 (1 mg/kg) and WAY 267,464 (10, 30, and 100 mg/kg). Given alone, SR49059 (1 mg/kg) and WAY 267,464 (30 and 100 mg/kg) impaired memory at a 30 min retention interval. The impairment with WAY 267,464 was not prevented by C25 (5 mg/kg), suggesting V1AR rather than OTR mediation of the effect. Given alone, C25 also impaired memory.
  
  
  CONCLUSIONS
  These results highlight a tonic role for endogenous AVP (and oxytocin) in social recognition memory and indicate that WAY 267,464 functions in vivo as a V1AR antagonist to prevent the memory-enhancing effects of AVP.
authors.affiliation: School of Psychology, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Callum
authors.initials: C
authors.lastname: Hicks
authors.forename: Linnet
authors.initials: L
authors.lastname: Ramos
authors.forename: Tristan A
authors.initials: TA
authors.lastname: Reekie
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Narlawar
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000819:agonists*; D021641:Recognition, Psychology / Q000187:drug effects*; D012919:Social Behavior; 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; D007211:Indoles; D011720:Pyrazoles; D011759:Pyrrolidines; D018045:Receptors, Oxytocin; D014667:Vasopressins; D001569:Benzodiazepines; C082134:relcovaptan