Evidence for distinct forms of compulsivity in the SAPAP3 mutant-mouse model for obsessive-compulsive disorder

The specific mechanisms underlying compulsive behavior in obsessive-compulsive disorder (OCD) are un-known. It has been suggested that such compulsivity may have its origin in cognitive dysfunction such as impaired processing of feedback information, received after the completion of goal-directed actions. The signal attenuation (SA) task models such a processing deficit in animals by attenuating the association strength between food reward and audiovisual feedback (signal) presented after performance of an operant response. The compulsive-like responding resulting from SA is well characterized in rats, but was so far not established in mice, a species for which powerful genetic OCD models exist. Thus, first, we demonstrate that the SA task can be implemented in mice and show that attenuation of reward-associated response feedback produces similar behavior in C57BL/6 mice as previously reported in rats. Second, we tested the hypothesis that SAPAP3 knock-out mice (SAPAP3-/-), prone to exhibit several OCD-like abnormalities including excessive grooming, show enhanced compulsive-like behavior in the SA task compared with their wild-type (WT) litter-mates. However, task-related compulsivity measures in SAPAP3-/- and WT did not yield significant differences, neither following SA nor during “regular” extinction of operant behavior. Thus, compulsive-like instrumental behavior following feedback distortion was not potentiated in compulsively grooming mice, implicating specifi-cally that (1) a general deficit in feedback processing is not related to excessive grooming in SAPAP3-/- and (2) different manifestations of compulsivity may be driven by independent mechanisms.