title: Antidepressant-like effects of ascorbic acid and ketamine involve modulation of GABAA and GABAB receptors.
abstract: BACKGROUND
  It has been suggested that dysregulation of γ-aminobutyric acid (GABA)-mediated neurotransmission is involved in the etiology of major depressive disorder and in the action of the fast-acting antidepressant ketamine. Considering that recent evidence has suggested that ascorbic acid may exert an antidepressant-like effect through mechanisms similar to ketamine, this study evaluated the involvement of GABAA and GABAB receptors in the antidepressant-like effect of ascorbic acid, comparing the results with those obtained with ketamine.
  
  
  METHODS
  To investigate the involvement of GABAA in the antidepressant-like effect of ascorbic acid and ketamine in the tail suspension test (TST), mice were treated with a sub-effective dose of ascorbic acid (0.1mg/kg, po), ketamine (0.1mg/kg, ip) or vehicle and 30minutes later, a sub-effective dose of muscimol (0.1mg/kg, ip, GABAA receptor agonist) or vehicle was administered. In another set of experiments, mice were treated with ascorbic acid (1mg/kg, po, active dose in the TST) or vehicle and 30minutes later, baclofen (1mg/kg, ip, GABAB receptor agonist) was administered. A similar experimental protocol was performed with ketamine (1mg/kg, ip).
  
  
  RESULTS
  The administration of muscimol combined with ascorbic acid or ketamine produced a synergistic antidepressant-like effect in the TST. Moreover, the antidepressant-like effects of ascorbic acid and ketamine were abolished by baclofen. There was no alteration in spontaneous locomotion in any experimental group.
  
  
  CONCLUSIONS
  Results indicate that the anti-immobility effect of ascorbic acid and ketamine in TST may involve an activation of GABAA receptors and a possible inhibition of GABAB receptors.
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Priscila B
authors.initials: PB
authors.lastname: Rosa
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Vivian B
authors.initials: VB
authors.lastname: Neis
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Camille M
authors.initials: CM
authors.lastname: Ribeiro
authors.affiliation: Post-Graduate Nutrition Program, Center of Health Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
authors.forename: Morgana
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil. Electronic address: alsrodri@gmail.com.
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019417:Hindlimb Suspension / Q000379:methods; D007649:Ketamine / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D007649:Ketamine; D001205:Ascorbic Acid
keywords: Ascorbic acid; Depression; GABA; Ketamine