Serotoninergic modulation of cortical and respiratory responses to episodic hypoxia

Biphasic respiratory response to hypoxia in anesthetized animals is accompanied by changes in the EEG mostly in the low EEG frequency bands. Serotonin is a potent modulator of cortical and respiratory activity through 5-HT(2) receptors. Present study investigated whether 5-HT(2) receptors might be involved in the EEG and respiratory relationship during normoxic and hypoxic respiration assessed from integrated phrenic (Phr) and hypoglossal (HG) nerve activities. EEG signal recorded from the frontal cortex was subjected to power spectral analysis in delta, theta, alpha, and beta frequency bands. Systemic administration of 5-HT(2) agonist DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) enhanced tonic and lowered peak phasic respiratory activity, and increased frequency of bursts of Phr and HG activity. At the same time, EEG activity became desynchronized and arterial blood pressure (ABP) increased. Following DOI pretreatment, 11% hypoxia induced an augmented respiratory response in comparison with the response in the baseline condition. ABP fell less then in the control hypoxia. EEG pattern changed less than in the baseline state. Subsequent administration of ketanserin, a 5-HT(2) antagonist increased respiratory activity, elicited a synchronization of EEG activity and hypotension. The respiratory response to hypoxia was attenuated and cortical response was more potent in comparison with that after DOI injection. Arterial blood pressure decreased more then during baseline hypoxic response. The results suggest that modulation of cortical synchronization and desynchronization through 5-HT(2) receptor active agents may impact to hypoxic respiratory response.