Serotoninergic modulation of cortical and respiratory responses to episodic hypoxia
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
Eur J Med Res (2009) 14(Suppl. IV): 32-37
December 7, 2009 © I. Holzapfel Publishers 2009
SEROTONINERGIC MODULATION OF CORTICAL AND RESPIRATORY RESPONSES TO EPISODIC HYPOXIA K. Budzinska
Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
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-HT2 receptors. Present study investigated whether 5-HT2 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-HT2 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 5HT2 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 5HT2 receptor active agents may impact to hypoxic respiratory response. Key words: serotonin 5-HT2 receptor, phrenic activity, hypoglossal activity, EEG, hypoxia
INTRODUCTION
Serotonin (5-HT) is present in the brainstem including the respiratory nuclei, phrenic and hypoglossal motoneurons [1]. Central respiratory activity is mostly mediated by 5HT1 and 5HT2 receptors. Moreover, serotonin drives directly hypoglossal motoneurons [2] and plays an important role in regulating hypoglossal motoneuron excitability via 5-HT2A receptors. Although present in the carotid bodies [3], serotonin
does not trigger the respiratory hypoxic response; however, at the level of the central respiratory system 5-HT influences dynamics of the respiratory response to hypoxia [4]. Brain serotoninergic system through G protein-coupled receptors is an important state-dependent neuromodulator. Serotonin immunoreactive fibers and terminals are demonstrated in the sensory and motor cortex. There is a rich representation of 5HT2A receptors in several cortical areas in frontal, parietal, temporal and occipital lobes predominantly in the Vth
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