title: Serotonergic system in hypoxic ventilatory response in unilateral rat model of Parkinson's disease.
abstract: BACKGROUND
  Malfunctioning 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-HT2receptors in the modulation of normoxic breathing and the hypoxic ventilatory response (HVR) in rat model of Parkinson's disease.
  
  
  METHODS
  Wistar 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.
  
  
  RESULTS
  Degeneration 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.
  
  
  CONCLUSIONS
  These 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-HT2receptors.
authors.affiliation: Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5, 02-106, Warsaw, Poland.
authors.forename: Kryspin
authors.initials: K
authors.lastname: Andrzejewski
authors.affiliation: Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Pawińskiego 5, 02-106, Warsaw, Poland. kkaczynska@imdik.pan.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczyńska
authors.affiliation: Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research (CePT), Medical University of Warsaw, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zaremba
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009928:Organ Specificity; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D000662:Amphetamines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D016627:Oxidopamine; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine
keywords: 6-OHDA rat model; DOI; Hypoxia; Ketanserin; Serotonergic 5-HT2 receptors