Ligand-specific effects of 5-HT2A receptor antagonists on fear extinction in C57BL/6J mice: Comparative insights from MDL 11,939 and MDL 100,907
bioRxiv (Cold Spring Harbor Laboratory) July 3, 2026 Anastasia Tyulmenkova, Robert W. Stackman
The 5-HT2A receptor antagonists MDL 11,939 and MDL 100,907 produce different effects on fear extinction in adult C57BL/6J mice. Acute administration of either antagonist increased freezing to the first conditioned stimulus, indicating enhanced fear expression. Repeated MDL 11,939 impaired extinction, increasing freezing across trials and the number of trials to reach criterion, while MDL 100,907 did not significantly alter extinction. Selective 5-HT2C antagonism with SB 242084 did not affect fear expression or extinction. These results suggest ligand-specific and dose-dependent effects of 5-HT2A receptor antagonism on fear extinction, possibly through distinct intracellular signaling pathways.