Abstract
BackgroundMalfunctioning of the serotonergic system in Parkinson’s disease may contribute to non-motor symptoms such as respiratory complications. Thus the aim of our study was to investigate the role of serotonin 5-HT2 receptors in the modulation of normoxic breathing and the hypoxic ventilatory response (HVR) in rat model of Parkinson’s disease.MethodsWistar rats were lesioned unilaterally with double 6-hydroxydopamine (6-OHDA) injection to the right medial forebrain bundle (MFB). Before lesion and two weeks later animals were put in whole body plethysmography chamber and exposed to hypoxia (8% O2). Before hypoxic tests animals received intraperitoneal injections of DOI and ketanserin. Efficacy of lesion was confirmed by cylinder test, assessing limb use asymmetry.ResultsDegeneration of the nigrostriatal pathway augmented response of tidal volume and minute ventilation to hypoxia. DOI administration in control and lesion state caused a significant rise in normoxic respiratory rate and minute ventilation. Yet, ventilatory response of these parameters to hypoxia was attenuated. Post-DOI magnitude of HVR in lesioned state was decreased in compare to pre-lesion control. Subsequent ketanserin injection reverted DOI-induced respiratory effects. We demonstrated that 6-OHDA treatment decreased the content of serotonin in the injured striatum and on both sides of the brainstem, leaving the concentration of noradrenaline on unchanged level.ConclusionsThese observations showed that damage of the nigrostriatal system initiates changes in the serotonergic system, confirmed by reduced concentration of serotonin in the striatum and brainstem, which affects the magnitude of respiratory response to hypoxia after activation of 5-HT2 receptors.
Highlights
Malfunctioning of the serotonergic system in Parkinson’s disease may contribute to non-motor symptoms such as respiratory complications
Animals lesioned with 6OHDA after first control hypoxia were treated intraperitoneally (i.p.) with DOI (2, 5-dimethoxy-4-iodoamphetamine) at a dose of 1.5 mg kg−1 and after 30 min they were exposed to second hypoxic test
The data were expressed as percentage of post-hypoxic change with reference to the normoxic values treated as a 100%
Summary
Malfunctioning of the serotonergic system in Parkinson’s disease may contribute to non-motor symptoms such as respiratory complications. The aim of our study was to investigate the role of serotonin 5-HT2 receptors in the modulation of normoxic breathing and the hypoxic ventilatory response (HVR) in rat model of Parkinson’s disease. Apart from the motor deficits patients with PD frequently exhibit non-motor symptoms, which significant are still often undiagnosed and untreated [3]. Among the latter are respiratory disturbances: restrictive pulmonary function, respiratory dysrhythmias and upper airway dysfunction [4, 5]. Chemical lesion of the raphe magnus, where serotonergic neurons are present, produced increased ventilatory response to hypoxia in awake rats [19]. Extensive damage of medullary 5-HT neurons in newborn piglets augmented respiratory rate response to hypoxia during sleep [20]
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