title: Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats.
abstract: Various evidence indicate that schizophrenia is a neurodevelopmental disorder. Epidemiological observations point to oxygen deficiencies during delivery as one of the early risk factors for developing schizophrenia. The aim of the present study was to examine the effect of postnatal anoxia in rats. Anoxia was experimentally induced by placing 9-day-old rat pups for 6 min in a chamber saturated with 100% nitrogen (N(2)). Exposure to anoxia on postnatal day (PND) 9 resulted in significantly reduced subcortical dopamine metabolism and turnover, as measured by striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported in schizophrenic patients. There was no effect of postnatal anoxia on either baseline or d-amphetamine-induced deficit in the prepulse inhibition (PPI) paradigm in adulthood. Accordingly, although oxygen deficiency early in life has been discussed as vulnerability factor in developing schizophrenia, exposure to postnatal anoxia in the rat does not show clear-cut phenomenological similarities with the disorder.
authors.affiliation: Department of Behavioural Pharmacology, NeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark. ksn@neurosearch.dk
authors.forename: Karin
authors.initials: K
authors.lastname: Sandager-Nielsen
authors.forename: Maibritt B
authors.initials: MB
authors.lastname: Andersen
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Sager
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.forename: Jørgen
authors.initials: J
authors.lastname: Scheel-Krüger
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000502:physiology*
chemical_list: D004298:Dopamine