Serotoninergic modulation of cortical and respiratory responses to episodic hypoxia

Abstract

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.

Figure 1

Changes in peak amplitude of integrated activity of phrenic (A Phr) and hypoglossal (HG) nerve and respiratory frequency (f) evoked 5 min after systemic injection of DOI and ketanserin (KS). Effects were calculated as a percent of control before administration of agents. All effects were significant, P < 0.05. Values are means ± SE, n = 8.

Figure 2

Effect of DOI and ketanserin (KS) administration on systolic (Sys) and diastolic (Dia) arterial blood pressure (ABP) and the maximal response to hypoxia (H) at baseline (C), after DOI and ketanserin. All effects were significant, P < 0.05. Values are means ± SE, n = 8.

Figure 3

Percent changes in power density of total EEG and delta, theta, beta, and alpha frequency bands elicited by DOI and ketanserin (KS). Horizontal line denotes the baseline values of power densities equal to 100%. Values are means ± SE, n = 8. All effects were significant save alpha power density after DOI administration.

Figure 4

Hypoxic effects on minute phrenic (Axf Phr) and hypoglossal activity (Axf HG) and respiratory frequency (f) divided into the phases of the response in baseline conditions and following DOI and ketanserin (KS) injection. Abbreviations: C - control value before induction of hypoxia, HS - hypoxic stimulation, HD - hypoxic decline, HA- hypoxic apnea, and R- recovery. Values are means ± SE, n = 8. *Significant difference between DOI and KS group; #significant difference between Baseline and DOI group; †significant difference between Baseline and KS group; P < 0.05.

Figure 5

Effects of hypoxia within the phases of the respiratory response on power density of total EEG and delta, theta, beta, and alpha frequency bands in baseline conditions and following DOI and ketanserin (KS) injection. Abbreviations same as in Fig 4. *Significant difference between DOI and KS group; #significant difference between Baseline and DOI group; †significant difference between Baseline and KS group; P < 0.05.