The BTBR T+ tf/J (BTBR) mouse models repetitive behaviors and restricted interests as observed in autism spectrum disorder (ASD). We recently demonstrated that BTBR mice exhibit a probabilistic reversal learning deficit compared to that of C57BL/6J (C57) mice. Risperidone, the most commonly prescribed FDA-approved drug to treat irritability in ASD, reduces repetitive self-grooming behavior in BTBR mice. Unknown is whether risperidone may be effective in treating other repetitive behaviors such as behavioral inflexibility.
Objectives:
The present experiment investigated whether acute risperidone treatment affects probabilistic reversal learning in a spatial discrimination test in BTBR and C57 mice.
Methods:
BTBR mice were tested on acquisition, retention and reversal learning of a spatial discrimination using a 80/20 probabilistic learning procedure. In the spatial discrimination, mice were trained to obtain a cereal reinforcement from one of two food wells placed in distinct locations within a rectangular-shaped maze. The “correct” choice was reinforced on 80% of trials and the “incorrect” choice was reinforced on 20% of trials. Twenty-four hours after completion of acquisition learning, mice received a retention test followed immediately by reversal learning. Mice received injections of 0, 0.06, or 0.12 mg/kg of risperdone 30 min prior to the reversal learning test. The learning criterion for the acquisition, retention and reversal learning phases were each 6 consecutive correct trials.
Results:
BTBR and C57 mice performed similarly in initial acquisition and retention of a spatial discrimination as previously observed. Vehicle-treated BTBR mice required significantly greater number of trials to achieve reversal learning criterion compared to that of C57 mice. Risperidone 0.12 mg, but not 0.06 mg, attenuated the reversal learning impairment in BTBR mice. Analysis of reversal learning errors, indicated that risperidone 0.12 mg treatment decreased regressive errors in BTBR mice, thus facilitating the maintaining of a new choice pattern after being initially selected.
Conclusions:
BTBR mice comparable to that observed in ASD individuals exhibit impairments in probabilistic reversal learning. The present findings indicate that acute risperidone treatement alleviates a reversal learning deficit in BTBR mice. Risperidone may serve as a potential treatment for reducing cognitive flexibility deficits in ASD.