| First Author | van den Boom BJG | Year | 2019 |
| Journal | Genes Brain Behav | Volume | 18 |
| Issue | 4 | Pages | e12557 |
| PubMed ID | 30688005 | Mgi Jnum | J:294973 |
| Mgi Id | MGI:6458233 | Doi | 10.1111/gbb.12557 |
| Citation | van den Boom BJG, et al. (2019) Behavioral flexibility in a mouse model for obsessive-compulsive disorder: Impaired Pavlovian reversal learning in SAPAP3 mutants. Genes Brain Behav 18(4):e12557 |
| abstractText | Obsessive-compulsive disorder (OCD) is characterized by obsessive thinking, compulsive behavior and anxiety, and is often accompanied by cognitive deficits. The neuropathology of OCD involves dysregulation of cortical-striatal circuits. Similar to OCD patients, SAPAP3 knockout mice 3 (SAPAP3(-/-) ) exhibit compulsive behavior (grooming), anxiety and dysregulated cortical-striatal function. However, it is unknown whether SAPAP3(-/-) display cognitive deficits and how these different behavioral traits relate to one another. SAPAP3(-/-) and wild-type (WT) littermates were trained in a Pavlovian conditioning task pairing visual cues with the delivery of sucrose solution. After mice learned to discriminate between a reward-predicting conditioned stimulus (CS+) and a non-reward stimulus (CS-), contingencies were reversed (CS+ became CS- and vice versa). Additionally, we assessed grooming, anxiety and general activity. SAPAP3(-/-) acquired Pavlovian approach behavior similarly to WT, albeit less vigorously and with a different strategy. However, unlike WT, SAPAP3(-/-) were unable to adapt their behavior after contingency reversal, exemplified by a lack of re-establishing CS+ approach behavior (sign tracking). Surprisingly, such behavioral inflexibility, decreased vigor, compulsive grooming and anxiety were unrelated. This study shows that SAPAP3(-/-) are capable of Pavlovian learning, but lack flexibility to adapt associated conditioned approach behavior. Thus, SAPAP3(-/-) not only display compulsive-like behavior and anxiety, but also cognitive deficits, confirming and extending the validity of SAPAP3(-/-) as a suitable model for the study of OCD. The observation that compulsive-like behavior, anxiety and behavioral inflexibility were unrelated suggests a non-causal relationship between these traits and may be of clinical relevance for the treatment of OCD. |
