The selective 5-HT2A receptor agonist 25CN-NBOH does not affect reversal learning in mice

Psychedelic 5-hydroxytryptamine 2A receptor (5-HT2AR) agonists are showing promise in the treatment of psychiatric disorders, such as treatment-resistant depression and anxiety. Human studies suggest that enhanced cognitive flexibility may contribute to their clinical efficacy. Both improvement and impairment of cognitive flexibility has been reported with 5-HT2AR ligands, making the link between 5-HT2AR pharmacology and cognitive flexibility equivocal. We tested the selective 5-HT2AR agonist 25CN-NBOH in healthy male C57BL/6JOlaHsd mice in a touchscreen-based mouse reversal learning test. No effects were observed on acquisition of the new stimulus-reward contingency, learning errors, or perseverative responses during reversal. Our results suggest that 25CN-NBOH does not affect reversal learning in the schedule used in this study.