title: The effect of central noradrenergic system lesion on dopamine (DA) and serotonin (5-HT) synthesis rate following administration of 5-HT3 receptor ligands in chosen parts of the rat brain.
abstract: BACKGROUND
  Since little has been known about the effect of the central noradrenergic system on the reactivity of serotonin 5-HT3 receptors, the aim of the current study was to find out whether this reactivity could be altered by chemical damage to the system in adult rats in early developmental stage.
  
  
  METHODS
  Adult male Wistar rats with central noradrenergic lesion induced by DSP-4 on day 1 and 3 of life were injected with analgesic model substance - morphine, serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide, PBG), 5-HT3 receptor antagonist (ondansetron) or both compounds jointly followed by decarboxylase inhibitor of aromatic amino acids (NSD-1050). After 30 min following NSD-1050 injection, the animals were decapitated using a guillotine. Chosen cerebral structures were dissected, and the contents of 5-hydroxytryptofan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA) were determined using high-pressure liquid chromatography with electrochemical detection (HPLC/ED).
  
  
  RESULTS
  Neither PBG nor morphine affected l-DOPA contents in the hippocampus in control rats; however, DSP-4 lesion caused a significant decrease in the synthesis rate of DA in this structure. Hippocampal contents of 5-HTP increased after morphine or PBG administration, and central noradrenergic lesion attenuated this effect. Morphine or PBG decreased cerebellar DA synthesis rate in control rats and DSP-4 lesion did not modify it. Cerebellar levels of 5-HTP increased after morphine or PBG challenge in control rats. DSP-4 lesion intensified the effect of morphine and attenuated that of PBG. Ondansetron abolished the effects mediated by PBG. We did not observe any impact of PBG or ondansetron on DA and 5-HT synthesis in the striatum.
  
  
  CONCLUSIONS
  Damage to the central noradrenergic system in rat newborns, through altered reactivity of central 5-HT3 receptors, results in permanent disorders in serotoninergic transmission in hippocampus and cerebellum as well as dopaminergic transmission in hippocampus, which may attenuate the activity of the descending pathways that derive from these structures.
authors.affiliation: The Dr. Janusz Daab Hospital of Trauma Surgery in Piekary Śląskie, Poland. Electronic address: wojciech_roczniak@interia.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Roczniak
authors.affiliation: The Jan Grodek Higher Vocational State School in Sanok, Medical Institute, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Babuśka-Roczniak
authors.affiliation: Department of Environmental Health and Epidemiology, Institute of Occupational Medicine in Sosnowiec, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kwapuliński
authors.affiliation: Chair and Department of Toxicology, Silesian Medical University of Katowice, Faculty of Pharmacy in Sosnowiec, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Brodziak-Dopierała
authors.affiliation: The Dr. Janusz Daab Hospital of Trauma Surgery in Piekary Śląskie, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Widuchowski
authors.affiliation: The Jan Grodek Higher Vocational State School in Sanok, Medical Institute, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Cipora
authors.affiliation: Department of Toxicology and Health Protection, Medical University of Silesia, Katowice, Poland.
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.affiliation: Department of Pediatrics in Zabrze, Medical University of Silesia in Katowice, Poland.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Oświęcimska
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism*; D001596:Benzylamines; D001645:Biguanides / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008024:Ligands; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009498:Neurotoxins; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000096:biosynthesis*; D058827:Serotonin 5-HT3 Receptor Agonists / Q000494:pharmacology*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D001596:Benzylamines; D001645:Biguanides; D008024:Ligands; D009498:Neurotoxins; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin; D007980:Levodopa; D017294:Ondansetron; D009020:Morphine; C012102:DSP 4; D004298:Dopamine; C008846:phenyl biguanide
keywords: 5-HT(3) receptor; Central noradrenergic system lesion; Dopamine; Serotonergic system; Serotonin