The Effect of 5-HT2C Receptor Activation on Nausea-Induced Behaviour in Rats

The present study aimed at investigating the role of the 5-HT2C receptor in nausea using different models of nausea-induced behaviour in rats. Two chemically distinct 5-HT2C agonists (lorcaserin and CP-809101) were evaluated using the conditioned gaping model. At therapeutically relevant doses, lorcaserin caused rats to display conditioned gaping reactions. This effect was successfully blocked by pre-treating the animals with the 5-HT2C antagonists SB-242084, suggesting that this receptor is involved in the genesis of nausea. In contrast, CP-809101 did not produce conditioned gaping in rats administered with doses higher than its efficacy range in feeding studies. These results suggest that the relevance of this receptor in nausea may be more complex than previously considered. It invites the question of whether functional selectivity may be the reason for the differences between side effect profiles of these two serotonergic drugs.