Abstract
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.
Highlights
Obsessive-compulsive disorder (OCD) is a mental disorder with a lifetime prevalence of 1–2%1
The normalized lever press rate did not differ between Sapap3-KO mice and WT littermates, suggesting that the lower lever press rate during valued testing could be explained by generally lower lever press performance in Sapap3-KO mice
Significant reward devaluation was evident in all training and feeding conditions. **p < 0.01, ***p < 0.001, valued vs. devalued session. (f) Lever press rates from valued and devalued test sessions normalized to the last RR20 training session or to the mean of the last three RI60 training sessions. **p < 0.01, ***p < 0.001, valued vs. devalued session. (g) The devaluation index differed significantly between RR- and RI-trained mice but not within RI-trained mice
Summary
Obsessive-compulsive disorder (OCD) is a mental disorder with a lifetime prevalence of 1–2%1. Habitual lever pressing can be induced in operant conditioning paradigms by random-interval (RI) training, whereas random-ratio (RR) training favors goal-directed lever pressing[9,10]. Under both training schedules, reward delivery requires lever pressing. Under RR schedules, rewards are delivered after varying numbers of lever presses These two schedules impose different contingencies of response and reward rates and facilitate either habitual (RI) or goal-directed (RR) lever pressing. Using these training schedules, the present study sought to determine optimal behavioral conditions for habit formation in wildtype (WT) mice. Testing different variables in WT mice allowed us to appraise habit formation in Sapap3-KO mice within the limits of maximal goal-directed and habitual behavior of WT mice in our laboratory setting
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