Risperidone and the 5-HT2A receptor antagonist M100907 improve probabilistic reversal learning in BTBR T + tf/J mice.
A new serotonin-blocking drug improved rule-switching in autism-model mice without the drowsiness caused by risperidone.
01Research in Context
What this study did
Scientists gave BTBR mice a task called probabilistic reversal learning. The mice had to learn which hole gave food, then switch when the rule changed.
They tested two drugs: risperidone and a new compound called M100907. Both target brain chemicals linked to autism.
The team watched if the drugs helped the mice switch rules faster, a skill many kids with autism find hard.
What they found
Both drugs helped the mice learn the new rule. They made fewer wrong choices after the switch.
M100907 worked without the sluggish side effects seen with risperidone. The mice stayed alert and moved normally.
This suggests blocking 5-HT2A receptors could improve flexibility while avoiding sedation.
How this fits with other research
Hudson et al. (2012) reviewed 33 autism drug trials. They found risperidone has solid evidence, which matches this study's positive result.
Brondino et al. (2016) looked at GABA drugs for autism and found weak evidence. This study shifts focus to serotonin receptors instead.
Jones et al. (1992) tested dopamine drugs in autistic children decades ago. Their crossover design inspired the mouse work, showing how old ideas spark new science.
Why it matters
If you work with kids who get stuck on routines, this points to new drug targets. M100907 or similar 5-HT2A blockers might reduce rigidity without the sleepiness of current meds. Watch for human trials testing these compounds.
Want CEUs on This Topic?
The ABA Clubhouse has 60+ free CEUs — live every Wednesday. Ethics, supervision & clinical topics.
Join Free →Ask the prescribing doctor if newer 5-HT2A drugs are an option for clients stuck on routines despite behavioral plans.
02At a glance
03Original abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with restricted interests and repetitive behaviors (RRBs). RRBs can severely limit daily living and be particularly stressful to family members. To date, there are limited options for treating this feature in ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in ASD, but less is known about whether it is effective in treating "higher order" RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor targets in which only a subset may be procognitive and others induce cognitive impairment. 5HT2A receptor blockade represents one promising and more targeted approach, as various preclinical studies have shown that 5HT2A receptor antagonists improve cognition. The present study investigated whether risperidone and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal learning performance in the BTBR T + tf/J (BTBR) mouse model of autism. The effects of these treatments were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, similar to one in which ASD individuals exhibit impairments, both risperidone (0.125 mg) and M100907 (0.01 and 0.1 mg) improved reversal learning in BTBR mice. Risperidone (0.125 mg) impaired reversal learning in B6 mice. Improvement in probabilistic reversal learning performance resulted from treatments enhancing the maintenance of the newly correct choice pattern. Because risperidone can lead to unwanted side effects, treatment with a specific 5HT2A receptor antagonist may improve cognitive flexibility in individuals with ASD while also minimizing unwanted side effects.
Autism research : official journal of the International Society for Autism Research, 2014 · doi:10.3389/neuro.08.001.2007