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WAY 267,464, a non-peptide oxytocin receptor agonist, impairs social recognition memory in rats through a vasopressin 1A receptor antagonist action

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Abstract

Rationale

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.

Objectives

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.

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Acknowledgments

Research was funded by two National Health and Medical Research Council (NHMRC) grants (1033444 and 1011518) to ISM. ISM has been supported by an Australian Professorial Fellowship from the Australian Research Council and is currently an NHMRC Principal Research Fellow. Animal experiments conducted in this study comply with the Australian code for the care and use of animals for scientific purposes.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. School of Psychology, The University of Sydney, Sydney, NSW, 2006, Australia

    Callum Hicks, Linnet Ramos & Iain S. McGregor

  2. School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia

    Tristan A. Reekie, Rajeshwar Narlawar & Michael Kassiou

  3. Faculty of Health Sciences, The University of Sydney, Sydney, NSW, 2006, Australia

    Michael Kassiou

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  1. Callum Hicks
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  2. Linnet Ramos
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  3. Tristan A. Reekie
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  4. Rajeshwar Narlawar
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  5. Michael Kassiou
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  6. Iain S. McGregor
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Correspondence to Iain S. McGregor.

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Hicks, C., Ramos, L., Reekie, T.A. et al. WAY 267,464, a non-peptide oxytocin receptor agonist, impairs social recognition memory in rats through a vasopressin 1A receptor antagonist action. Psychopharmacology 232, 2659–2667 (2015). https://doi.org/10.1007/s00213-015-3902-5

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  • DOI: https://doi.org/10.1007/s00213-015-3902-5

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