OAKESHOTT S, PORT R, SUTPHEN J, WATSON-JOHNSON J, RAMBOZ S, KWAK S, HOWLAND D, BRUNNER D.
In an operant test R6/2 transgenic mice (240-CAG repeats, B6 congenic background) were less able to acquire lever pressing than control animals at an age where motor function is only mildly affected (from 9 weeks), with this deficit being both more pronounced and detected earlier (from 5 weeks) where reinforcement was not solely contingent on responding. BAC HD mice, which typically reveal a less severe behavioral phenotype than the R6/2 line, did not show a deficit in the acquisition of a simple lever press. However, motivational abnormalities were again found using more complex operant paradigms: BAC HD mice were as or more willing than age-matched control mice to work on a low-effort task (an FR5 schedule) for food reinforcement, but stopped responding more rapidly than did controls when the effort required for reinforcement increased (a progressive ratio task). These data indicate that these mouse models recapitulate the apathy seen in HD patients, and point to a potentially valuable preclinical screening assay.