Aberrant habit formation in the Sapap3-knockout mouse model of obsessive-compulsive disorder

Sci Rep. 2019 Aug 19;9(1):12061. doi: 10.1038/s41598-019-48637-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • Disease Models, Animal
  • Genotype
  • Habits*
  • Locomotion
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Obsessive-Compulsive Disorder / diagnosis*
  • Obsessive-Compulsive Disorder / etiology*
  • Phenotype
  • Reward


  • Nerve Tissue Proteins
  • Sapap3 protein, mouse