Aberrant habit formation in the Sapap3-knockout mouse model of obsessive-compulsive disorder
Open accessAbstract
Motor behavior can be executed deliberately to achieve specific goals. With repetition, such behavior can become habitual and noncontingent on actions-outcomes. The formation of habits is a natural process that can become pathological, such as in obsessive-compulsive disorder (OCD). The present study used the Sapap3-knockout (KO) mouse model of OCD to assess habit formation based on reward devaluation. We also tested wildtype mice under different training and food-restriction schedules to assess the extent of natural habit formation. We found that Sapap3-KO mice were insensitive to the devaluation of a sucrose reward under conditions in which wildtype littermates were sensitive to devaluation. Moreover, food restriction favored goal-directed action in wildtype mice, whereas mice that were fed ad libitum were more likely to form habitual behavior but nevertheless maintained partly goal-directed lever-press behavior. In conclusion, only Sapap3-KO mice developed behavior that was fully insensitive to reward devaluation, suggesting that pathological habits in OCD patients are recapitulated in the present Sapap3-KO mouse model. In wildtype mice, the extent of habit formation was influenced by the state of satiety during training and the reinforcement schedule.
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Sapap3-KO mice exhibit deficits in the balance of habitual and goal-directed behavior.
“Such phenotypes are excessive grooming [9][10][11], anxiety-like behavior [9,12], behavioral inflexibility [13,14], and deficits in the balance of habitual and goal-directed behavior [15,16].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [15]
Young adult Sapap3-KO mice have lower locomotor activity in an open-field arena.
“Previously we made the observation that young adult Sapap3-KO mice have lower locomotor activity in an open-field arena [15].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [15]
Altered synaptic properties at the Cg1/M2-to-DMS input could underlie OCD-like behavioral inflexibility leading to aberrant habit formation.
“Altered synaptic properties at this input could underlie OCD-like behavioral inflexibility leading to aberrant habit formation [15] since lesioning the M2 impairs goal-directed behavior [46].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [15]
A devaluation index score of 1 suggests perfect goal-directed behavior; a score of 0 is habitual.
“A devaluation index score of 1 suggests perfect goal-directed behavior85,95. In contrast, a score of 0 is habitual.”
From Revealing abrupt transitions from goal-directed to habitual behavior (2026) · cites this paper as [95]
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- Authors
- Hadjas, L. C., Lüscher, C., & Simmler, L. D.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Simmler, Linda D.
- Venue
- Scientific Reports
- Published
- 2019-08-19
- Volume
- 9
- Issue
- 1
- Pages
- 12061-12061
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6700199
- OpenAlex
- W2967156799
- Cited by
- 56
- References
- 22
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 14 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 2
- FWCI
- 7.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (170266, 186266, 174178, 164751)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- obsessive-compulsive disorder, habit formation, reward devaluation, goal-directed behavior, dietary restriction, satiety, reinforcement schedules, sucrose reward, mouse model
- MeSH terms
- Animals, Behavior, Animal, Disease Models, Animal, Genotype, Habits, Locomotion, Nerve Tissue Proteins, Obsessive-Compulsive Disorder, Phenotype, Reward, Mice, Knockout, Mice
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