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Gender Differences in Response to Oxytocin in C57BL/6N Mice

Friday, 3 May 2013: 15:15
Chamber Hall (Kursaal Centre)


Background: Oxytocin has been proposed as a possible treatment for neurodevelopmental conditions such as autism spectrum disorders. However many preclinical studies have a male bias, and often only examine a single dose and single behaviour test. 

Objectives:  We planned a systematic study of the behavioural effects of single and repeated doses of oxytocin in male and female C57/B6N mice. 

Methods:  The C57/B6N mouse strain was selected because it exhibits behaviours, such as low levels of prepulse inhibition of startle (PPI), that are also found in neurodevelopmental conditions such as autism spectrum disorder. The behavioural test battery comprised tasks that have been reported to be disrupted in animal models of neurodevelopmental disorders:  PPI; novel object recogition; social interaction; and open field with amphetamine challenge. Each animal was tested in one test per week over a period of 4 weeks. Low (10ug/kg), mid (100ug/kg) and high (1000ug/kg) dose oxytocin or saline control was administered as a single or repeated sub-cutaneous dose prior to each task.  

Results: Preliminary analyses suggest that the effects of oxytocin may be cumulative over repeated exposures and observed at lower doses in female mice than male mice. Baseline PPI was lower in male mice than females. Although oxytocin disrupted PPI in female mice, it improved PPI in male mice. Oxytocin improved object recognition memory in female mice but disrupted object recognition memory in male mice. In both genders oxytocin increased social interaction time and suppressed the amphetamine locomotor response. 

Conclusions:  Thus, oxytocin generally ‘improved’ behaviours reported to be impaired in models of neurodevelopmental disorders. Female mice tended to be more sensitive to lower doses of oxytocin, whereas male mice responded only when the dose of oxytocin reached mid or high levels. In translation, careful investigation of how gender influences dose response in the clinical population is needed.

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