Nitrergic, glutamatergic and gabaergic systems in lithium toxicity

Yamanturk-Celik P., Unlucerci Y., Sevgi S., Bekpinar S., Eroglu L.

JOURNAL OF TOXICOLOGICAL SCIENCES, vol.37, no.5, pp.1017-1023, 2012 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 37 Issue: 5
  • Publication Date: 2012
  • Doi Number: 10.2131/jts.37.1017
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1017-1023
  • Istanbul University Affiliated: Yes


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 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.