Research reportDifferential effects of 5-HT2A and 5-HT2C receptor blockade on strategy-switching

Recent experiments indicate that blockade of serotonin (5-HT) 2A and 2C receptors have differential effects on reversal learning. The present experiments investigated the effects of the 5-HT2A receptor antagonist, ketanserin and 5-HT2C receptor antagonist, SB242084 on acquisition and strategy-switching in a visual cue-response paradigm. Long-Evans rats were trained in a cross-maze to enter an arm based on color (visual cue version) or a specific turn response (response version). Systemic treatment with ketanserin did not affect initial learning of a visual cue or response discrimination, but ketanserin at 0.5 mg/kg significantly enhanced a switch between visual cue and response strategies. Ketanserin facilitated strategy-switching by inhibiting responses to a previously relevant strategy without affecting choices to never-reinforced strategies. Treatment with SB242084 (0.5, 1.0 or 2.0 mg/kg) did not affect acquisition of a visual cue or response discrimination. SB242084 treatment also did not affect strategy-switching. The present findings suggest that blockade of 5-HT2A, but not 5-HT2C, receptors enhance strategy switching.

Research highlights▶ Ketanserin treatment enhances strategy switching. ▶ Ketanserin enhances strategy switching by reducing regressive errors. ▶ Prazosin does not affect strategy switching. ▶ SB242084 does not affect strategy switching.