title: Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression.
abstract: OBJECTIVE
  We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine.
  
  
  METHODS
  Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration.
  
  
  RESULTS
  L-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by L-arginine.
  
  
  CONCLUSIONS
  Both the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.
authors.affiliation: 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Risskov,Denmark.
authors.forename: Nico
authors.initials: N
authors.lastname: Liebenberg
authors.affiliation: 2Department of Physics and Cemistry,School of Pharmceutical Sciences of Ribeirão Preto,University of São Paulo,Ribeirão Preto,São Paulo,Brazil.
authors.forename: Sâmia
authors.initials: S
authors.lastname: Joca
authors.affiliation: 1Translational Neuropsychiatry Unit,Department of Clinical Medicine,Aarhus University,Risskov,Denmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
mesh_terms: D000778:Anesthetics, Dissociative / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D000778:Anesthetics, Dissociative; D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D007649:Ketamine; D001120:Arginine; D006152:Cyclic GMP
keywords: NOS activity