Deletion of the 5-HT3A receptor reduces behavioral persistence and enhances flexibility
image: Mice navigating operant conditioning tasks to test behavioral persistence.
Credit: Osaka Metropolitan University
The 5-HT3A receptor is the only ionotropic serotonin receptor and has been implicated in cognitive functions, yet its specific role remains unclear. To investigate the contribution of the 5-HT3A subtype, an Osaka Metropolitan University-led research team trained wild-type and 5-HT3A receptor knockout mice across a series of operant conditioning tasks and compared their behavioral performance. Following nose-poke training, both groups underwent a rule-switching task, extinction tests under fixed ratio and variable ratio reinforcement schedules, and a progressive ratio task to assess persistence.
The researchers found that 5-HT3A receptor knockout mice exhibited reduced responding during the extinction, suggesting diminished behavioral persistence. The progressive ratio task result, in which knockout mice showed a trend toward reduced responding, also supports this interpretation. Notably, however, knockout mice acquired the new rule in the switching task significantly faster than wild-type controls, indicating enhanced cognitive flexibility.
These findings suggest that the 5-HT3A receptor plays a role in regulating the balance between behavioral persistence and flexibility, normally biasing this balance toward persistence under normal physiological conditions. This mechanism may underlie the therapeutic effect of 5-HT3A receptor antagonists in treatment-resistant obsessive-compulsive disorder.
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