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• W2915040738 abstract "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." @default.
• W2915040738 created "2019-02-21" @default.
• W2915040738 creator A5010458603 @default.
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• W2915040738 date "2019-02-27" @default.
• W2915040738 modified "2023-10-14" @default.
• W2915040738 title "Behavioral flexibility in a mouse model for obsessive‐compulsive disorder: Impaired Pavlovian reversal learning in SAPAP3 mutants" @default.
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• W2915040738 doi "https://doi.org/10.1111/gbb.12557" @default.
• W2915040738 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6487954" @default.
• W2915040738 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30688005" @default.
• W2915040738 hasPublicationYear "2019" @default.
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