The role of cognitive and affective processing in a transgenic mouse model of cortical-limbic neuropotentiated compulsive behavior

Obsessive compulsive disorder (OCD) may involve abnormal cortical-limbic processing or responsiveness. Mice with behaviors resembling the symptoms of OCD and related disorders were made by expression of a neuropotentiating cholera toxin (CT) transgene in cortical-limbic D1 receptor-expressing neurons. Because these D1CT mice express CT in the piriform cortex and amygdala (major cognitive and affective olfactory processing areas) it was tested whether abnormal odor perception, discrimination, or responsiveness facilitates their compulsion-like behavior. The mice exhibited normal olfactory discriminative capability. An anxiogenic odor potentiated their abnormal repetitive leaping, but novel or familiar nonthreatening odors did not. These data suggest that compulsions can be triggered not by impaired cortical-limbic processing but by increased cortical-limbic responsiveness, particularly to sensory or cognitive stimuli with affective properties.