5-HT2C-like receptors in the brain of Xenopus laevis initiate sex-typical fictive vocalizations.

Vocalizations of male and female African clawed frogs (Xenopus laevis) are generated by brain stem central pattern generators. Serotonin (5-HT) is likely important for vocal initiation because, when applied in vitro, sex-typical fictive vocalizations are evoked from isolated brains. To explore the mechanisms underlying vocal initiation, we identified the types of serotonin receptors mediating vocal activation pharmacologically using a whole brain, fictive preparation. The results showed that 5-HT(2C)-like receptors are important for activation of fictive vocalizations in the sexes. 5-HT(2C) receptor agonists elicited fictive vocalizations, and 5-HT(2C) receptor antagonists blocked 5-HT-induced fictive vocalizations, whereas agonists and antagonists of 5-HT(2A) and 5-HT(2B) receptors failed to initiate or block 5-HT-induced fictive vocalizations in the sexes. The results indicate that serotonin initiates fictive vocalizations by binding to 5-HT(2C)-like receptors located either within or upstream of the vocal central pattern generator in both sexes. We conclude that the basic mechanism of vocal initiation is shared by the sexes despite the differences in the actual vocalizations between males and females. Sex-typical vocalizations, therefore, most likely arise from activation of different populations of 5-HT(2C) receptor expressing cells or from differential activation of downstream pattern generating neurons.