title: Differential levels of brain amino acids in rat models presenting learned helplessness or non-learned helplessness.
abstract: BACKGROUND
  Glutamatergic and γ-aminobutyric acid (GABA)ergic abnormalities have recently been proposed to contribute to depression. The learned helplessness (LH) paradigm produces a reliable animal model of depression that expresses a deficit in escape behavior (LH model); an alternative phenotype that does not exhibit LH is a model of resilience to depression (non-LH model).
  
  
  OBJECTIVE
  We measured the contents of amino acids in the brain to investigate the mechanisms involved in the pathology of depression.
  
  
  METHODS
  LH and non-LH models were subjected to inescapable electric footshocks at random intervals following a conditioned avoidance test to determine acquirement of predicted escape deficits. Tissue amino acid contents in eight brain regions were measured via high-performance liquid chromatography.
  
  
  RESULTS
  The non-LH model showed increased GABA levels in the dentate gyrus and nucleus accumbens and increased glutamine levels in the dentate gyrus and the orbitofrontal cortex. The LH model had reduced glutamine levels in the medial prefrontal cortex. Changes in the ratios of GABA, glutamine, and glutamate were detected in the non-LH model, but not in the LH model. Reductions in threonine levels occurred in the medial prefrontal cortex in both models, whereas elevated alanine levels were detected in the medial prefrontal cortex in non-LH animals.
  
  
  CONCLUSIONS
  The present study demonstrates region-specific compensatory elevations in GABA levels in the dentate gyrus and nucleus accumbens of non-LH animals, supporting the implication of the GABAergic system in the recovery of depression.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan. kmuneoka@med.showa-u.ac.jp
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Muneoka
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Shirayama
authors.forename: Mao
authors.initials: M
authors.lastname: Horio
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006380:Helplessness, Learned; D008297:Male; D023421:Models, Animal; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000596:Amino Acids; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid