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

Obsessive compulsive disorder (OCD) may involve abnormal cortical-limbic pr ocessing or responsiveness. Mice with behaviors resembling the symptoms of OCD and related disorders were made by expression of a neuropotentiating ch olera toxin (CT) transgene in cortical-limbic D1 receptor-expressing neuron s. Because these D1CT mice express CT in the piriform cortex and amygdala ( major cognitive and affective olfactory processing areas) it was tested whe ther abnormal odor perception, discrimination, or responsiveness facilitate s their compulsion-like behavior. The mice exhibited normal olfactory discr iminative capability. An anxiogenic odor potentiated their abnormal repetit ive 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.