title: Nitrergic, glutamatergic and gabaergic systems in lithium toxicity.
abstract: We examined the role of nitrergic, glutamatergic and gamma-aminobutyric acid (GABA)-ergic systems in the mechanism(s) underlying lithium induced acute toxicity. With this aim, lithium  (18 mEq/kg, i.p.) intoxicated rats were observed for 3 hr recording their clinical signs and death.  Lithium exposure at the dose used produced central nervous system (CNS) depression. Pre-treatment of N(w)-nitro-L-arginine methyl ester (L-NAME) a nonselective nitric oxide synthase inhibitor (10 mg/kg, i.p.), 7-nitroindazole (7-NI) a selective neuronal nitric oxide synthase inhibitor (25 mg/kg, i.p.), nitric oxide precursor L-arginine (1,000 mg/kg, i.p.) and MK-801 a noncompetitive antagonist of N-methyl-D-aspartic acid class of glutamate receptors (0.5 mg/kg, i.p.) all increased CNS depression and mortality in lithium group however, no change was seen in GABA receptor agonist GABA (1,000 mg/kg, i.p.) or D-arginine (1,000 mg/kg, i.p.) a biologically inactive enantiomer of L-arginine pre-treated rats. Glutamic acid decarboxylase (GAD) enzyme activity was measured in hippocampus, cerebral cortex and cerebellum of the different groups of animals. GAD enzyme activity reduced in cerebral cortex but not altered in hippocampus or cerebellum by lithium as compared to the control (saline) group. We conclude that an interaction with nitrergic and glutamatergic systems may have a role in the acute toxicity of lithium in rats.The inhibition of glutamate metabolism may arise from this interaction and the involvement of GABA-ergic system should be further investigated in this toxicity.
authors.affiliation: Department of Medical Pharmacology, Istanbul Faculty of Medicine, Istanbul University, Turkey. yamanturkp@yahoo.com
authors.forename: Pınar
authors.initials: P
authors.lastname: Yamantürk-Çelik
authors.forename: Yeşim
authors.initials: Y
authors.lastname: Unlüçerçi
authors.forename: Serhan
authors.initials: S
authors.lastname: Sevgi
authors.forename: Seldağ
authors.initials: S
authors.lastname: Bekpinar
authors.forename: Lütfiye
authors.initials: L
authors.lastname: Eroğlu
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D018021:Lithium Chloride / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018682:GABA Agents; D007191:Indazoles; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D019001:Nitric Oxide Synthase; D018021:Lithium Chloride; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester