Instrumental learning in a mouse model for obsessive-compulsive disorder: Impaired habit formation in Sapap3 mutants
Abstract
It has been hypothesized that maladaptive habit formation contributes to compulsivity in psychiatric disorders such as obsessive-compulsive disorder (OCD). Here, we used an established animal model of OCD, Sapap3 knockout mice (SAPAP3-/-), to investigate the balance of goal-directed and habitual behavior in compulsive individuals and if altered habit formation is associated with compulsive-like behavior. We subjected 24 SAPAP3-/- and 24 wildtype littermates (WT) to two different schedules of reinforcement in a within-subjects design: a random-ratio (RR) schedule to promote goal-directedness, and a random-interval (RI) schedule, known to facilitate habitual responding. SAPAP3-/- acquired responding under both schedules, but showed lower response rates and fewer attempts to collect food pellets than WT, indicative of altered reward processing. As expected, WT were sensitive to sensory-specific satiety (outcome devaluation) following RR training, but not RI training, demonstrating schedule-specific acquisition of goal-directed and habitual responding, respectively. In contrast, SAPAP3-/- were sensitive to outcome devaluation after both RR and RI training, suggesting decreased engagement of a habitual response strategy. No linear relation was observed between increased grooming and behavior during the outcome devaluation test in SAPAP3-/-. Together, our findings demonstrate altered reward processing and impaired habit learning in SAPAP3-/-. We report a diminished propensity to form habits in these mice, which albeit inconsistent with the predominant idea of excessive habit formation in OCD, nonetheless points at dysregulation of behavioral automation in the context of compulsivity. Thus, the habit hypothesis of compulsivity should be updated to state that an imbalance of habitual and goal-directed responding in either direction can contribute to the development of compulsive behavior.
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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 [16]
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- Authors
- Ehmer, I., Feenstra, M., Willuhn, I., & Denys, D.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Willuhn, I.
- ORCID
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 168
- Pages
- 107162
- ISSN
- 1074-7427 (ISSN-L)
- OpenAlex
- W3000022704
- Cited by
- 37
- References
- 43
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 3 · 2019: 1
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (2015/06367/ALW, 864.14.010, ERC-2014-STG 638013)
- Nederlands Herseninstituut
- 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, goal-directed behavior, compulsivity, outcome devaluation, sensory-specific satiety, reward processing, random-ratio schedules, random-interval schedules, grooming
- MeSH terms
- Animals, Conditioning, Operant, Disease Models, Animal, Female, Habits, Male, Nerve Tissue Proteins, Obsessive-Compulsive Disorder, Reward, Mice, Knockout
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