title: Postnatal morphine administration alters hippocampal development in rats.
abstract: Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, Minnesota, USA. ctraudt@uw.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Traudt
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkac
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Ennis
authors.forename: Leah M
authors.initials: LM
authors.lastname: Sutton
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Mammel
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Rao
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D011522:Protons; D009020:Morphine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D001973:Bromodeoxyuridine