The solely response of superficial RTN/pFRG chemoreceptors. Further experiments are required to examine whether the SERT-expressing and 5-HTcontaining neurons in the vicinity of the RTN/pFRG area are actual 5-HT neurons able to synthesize 5-HT or glutamatergic RTN/pFRG neurons expressing SERT and up-taking 5-HT. Nevertheless, fluoxetine blockade of 5-HT uptake may affect the 5-HT levels, the pH response of brainstem chemoreceptors and the RRG activity and responsiveness. Application of 5-HT to RTN/pFRG chemoreceptors increases their baseline level but not the magnitude of their response to pH. Thus, the abolition of the PBf responses to acidosis by fluoxetine cannot be simply explained by a decreased chemosensitivity of RTN/pFRG neurons and it possibly reflects more complex, 5-HT dependent mechanisms affecting the whole chemosensitive system. Within the maturing CNS, endogenous 5-HT acts through a plethora of receptors subtypes to modulate maturational processes, synaptic mechanisms and neuronal excitability. Similarly 5-HT exerts multiple effects on the neonatal respiratory network, Navitoclax facilitating the RRG via 5-HT1A receptors, depolarizing and firing the phrenic motoneurons via 5-HT2A receptors and reducing the transmission of the respiratory drive to motoneurons via 5-HT1B receptors. An excess of endogenous 5-HT affects the expression of 5-HT1A receptors, the RRG modulation by 5-HT and may also affect non-5HT systems known to modulate the RRG such as the catecholaminergic system. In addition, 5-HT may affect the gap junction coupling. Gap junction coupling occurs between cultured chemoreceptors as well as between chemoreceptors of discrete brainstem areas such as the locus coeruleus, the raphe and the RTN/pFRG. Frequent gap junctions contribute to the synchronous firing of raphe neurons and may lead the brainstem chemoreceptors to behave as a syncytium. Blockade of gap junctions reduces the in vivo RTN/pFRG chemosensitivity and the in vitro resting PBf. Interestingly, the gap junction coupling is reduced by excess of 5-HT. We therefore speculate that the fluoxetine-induced excess of 5-HT reduces the gap junction coupling between brainstem chemoreceptors and that a disorganized chemoreceptor drive to the RRG during acidosis may affect the PBf response. Thus, the fluoxetine-induced excess of 5-HT may directly and indirectly affect the RRG responsiveness to acidosis as well as the elaboration of the chemoreceptor drive. Although further experiments are required to decipher these different, non-exclusive mechanisms, data from several lines of transgenic mice further support a link between 5-HT and RRG response to CO2/pH. Indeed, genetically-induced alterations of the 5-HT system in mice affect the RRG responses to CO2/pH.