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Social Behaviour Is Altered in the Insulin-Regulated Aminopeptidase Knockout Mouse

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2019

Behav Brain Res 2019 Dec 30;376:112150. doi: 10.1016/j.bbr.2019.112150. Epub 2019 Aug 13.

Social Behaviour Is Altered in the Insulin-Regulated Aminopeptidase Knockout Mouse

P Burns;J Bowditch;J McFadyen;R Loiacono;AL Albiston;V Pham;SY Chai

Monash Biomedicine Discovery Institute, Department of Physiology, Department of Pharmacology, Monash University, Clayton, Victoria, Australia. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.

Service type: Knockout mice

Abstract

Oxytocin, and the closely related neuropeptide, vasopressin, are both known to modulate social behaviours. The pro-social effects of oxytocin are well-documented and have generated much interest into its suitability as a therapeutic for disorders characterised by social dysfunction. This study investigated the social phenotype of mice with a targeted deletion of the gene for insulin-regulated aminopeptidase, an enzyme involved in the degradation of oxytocin and vasopressin. In the 3-chamber sociability test, a genotype effect was observed and subsequent post hoc analysis revealed that male, but not female, insulin-regulated aminopeptidase knockout mice made significantly more approaches to the enclosure holding a stranger mouse than did wildtype mice (p = 0.0039). Male insulin-regulated aminopeptidase knockout mice also displayed decreased rearing (t = 2.309, df = 24, p = 0.0299) and locomotor activity (t = 2.134, df = 24, p = 0.043) in the open field test, suggestive of a reduced stress response to a novel environment. Our findings provide support for the role of insulin-regulated aminopeptidase in influencing social behaviour, possibly via modulation of oxytocin and vasopressin levels. The increase in social interaction observed in the male, but not female, insulin-regulated aminopeptidase knockout mice is in agreement with reports of sex differences in effects of oxytocin and vasopressin on social behaviours and should be explored further.

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