title: Two Chronic Stress Models Based on Movement Restriction in Rats Respond Selectively to Antidepressant Drugs: Aldolase C As a Potential Biomarker.
abstract: BACKGROUND
  Clinically depressed individuals respond to different types of antidepressants, suggesting that different neurobiological mechanisms may be responsible for their depression. However, animal models to characterize this are not yet available.
  
  
  METHODS
  We induced depressive-like behaviors in rats using 2 different chronic stress models: restraint in small cages or immobilization in adaptable plastic cones. Both models increased anxiety responses evaluated by novelty-suppressed feeding and the elevated plus-maze; increased learned helplessness evaluated by the tail suspension and forced swimming tests; and increased anhedonia evaluated by the sucrose preference test.
  
  
  RESULTS
  We assessed the ability of 2 different types of antidepressants to ameliorate depressive-like behaviors. We administered the serotonin reuptake inhibitor fluoxetine or the noradrenaline reuptake inhibitor reboxetine once daily for 28 days to rats that received either chronic restraint or immobilization stress, or no stress. Behavioral analysis revealed that fluoxetine ameliorated depressive-like behaviors when induced by chronic restraint stress, whereas reboxetine ameliorated these behaviors when induced by chronic immobilization stress. To further test biological differences between both models, we evaluated the levels of Aldolase C, an enzyme expressed by forebrain astrocytes that is regulated by antidepressant treatment, in the cerebrospinal fluid: chronic restraint stress, but not immobilization stress, increased the levels of Aldolase C. Moreover, the presence of astrocyte-derived Aldolase C-GFP in the cerebrospinal fluid indicates its central origin.
  
  
  CONCLUSIONS
  Two stress paradigms induced depressive-like behaviors that were sensitive to different antidepressant treatments. Biomarkers such as Aldolase C could help determine optimal antidepressant treatments for clinically depressed patients.
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Estibaliz
authors: E
authors: Ampuero
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Alejandro
authors: A
authors: Luarte
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Marcos
authors: M
authors: Santibañez
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Manuel
authors: M
authors: Varas-Godoy
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Jorge
authors: J
authors: Toledo
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Gabriela
authors: G
authors: Diaz-Veliz
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: Gabriel
authors: G
authors: Cavada
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy).
authors: F Javier
authors: FJ
authors: Rubio
authors: Facultad de Medicina, Universidad de los Andes, Chile (Dr Ampuero, Mr Luarte, Dr Santibañez, Mr Toledo, Drs Varas-Godoy, Cavada, Rubio, and Wyneken); Laboratorio de Neurobiologia, Centro de Investigaciones Biomedicas, Universidad Andres Bello, Santiago, Chile (Dr Ampuero); Facultad de Medicina, Universidad de Chile (Dr Diaz-Veliz); Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden (Dr Varas-Godoy). uwyneken@uandes.cl.
authors: Ursula
authors: U
authors: Wyneken
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002908:Chronic Disease; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology*; D005634:Fructose-Bisphosphate Aldolase / Q000134:cerebrospinal fluid* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D012149:Restraint, Physical; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology; D013315:Stress, Psychological
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D005634:Fructose-Bisphosphate Aldolase; D049452:Green Fluorescent Proteins; D009025:Morpholines; D000077593:Reboxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors
keywords: Fluoxetine; chronic stress; immobilization; reboxetine; restraint