Quantitative Assessment of Social Motivation in Mouse Models Relevant to Autism

Background:  Research on mouse models relevant to autism will benefit from the development of novel assays of complex social behavior including social motivation. The BTBR inbred mouse strain has previously demonstrated deficits in social behavior among other behaviors that provide some face validity to autism. Comparisons of BTBR mice to the prosocial B6 mice are therefore a reasonable means to validate the assessment of social motivation using novel paradigms. These novel measures can then be used to assess social motivation in mouse models relevant to autism. In recent years, the serotonin and oxytocin systems have been linked to autism. We are therefore exploring the role of these neurotransmitters in social motivation by testing mice lacking the serotonin transporter gene (SERT KO) and mice administered either an oxytocin agonist or antagonist.

Objectives:  The goals of this research are to develop and validate new quantitative measures of social motivation in mice and to use these paradigms to assess social motivation in mouse models relevant to autism. Two operant conditioning paradigms that allow a test mouse to control access to another mouse have been developed. Initial research involved testing with BTBR T + tf/J (BTBR) and C57BL/6J (B6) mouse strains for validation purposes. Additional studies are being carried out to determine the role of serotonin and oxytocin systems in social motivation.  

Methods:  In the social motivation task, test mice are trained to press a lever for a social reward in the form of 15s access to an unfamiliar stimulus mouse. The social reward is set on a progressive ratio schedule with a step size of three. The number of lever presses achieved in the final trial of a testing session (breakpoint) is used as an index of social motivation. In the valence comparison task, motivation for a food reward is compared to a social reward. The mice were conditioned to associate one lever consistently with a food reward and another consistently with the same social reward described in the previous paradigm.

Results:   All 9 B6 mice successfully learned to lever press for a social reward, but only 9 of 17 BTBR mice made this learned association. Comparisons between mice that completed testing revealed that BTBR mice had a significantly lower breakpoint than B6 mice (t=2.741, df=16, p=.015), indicating lower social motivation in these mice. However, in the valence comparison task, the BTBR mice also obtained significantly fewer food rewards than B6 mice (t=3.321, df=16, p=.004) suggesting that they may have a general deficit in motivation. Testing with the other mouse models is ongoing. In addition to the above novel quantitative measures of social motivation, assessments of social interest and social memory are being conducted through the use of the ANYMAZE video tracking system.

Conclusions: BTBR mice were found to have low levels of social motivation in comparison to B6 controls. However, the BTBR mice also demonstrated significantly fewer lever presses for a food reward in the valence comparison task suggesting low levels of motivation in general.