title: Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.
abstract: BACKGROUND
  In response to stress, corticotropin releasing hormone (CRH) and vasopressin (AVP) are released from the hypothalamus, activate their receptors (CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropic hormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states.
  
  
  OBJECTIVE
  The objective of the study is to assess the role of AVP and CRH receptors in fluoxetine and venlafaxine effects on the expression of depression-related behavior.
  
  
  METHODS
  In an animal model of depression (olfactory bulbectomy in mice, OB), we evaluated the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronic administration on depression-related behavior in the tail suspension test. Plasma levels of AVP, CRH, and ACTH were determined as well as participation of their receptors in the expression of depression related-behavior and gene expression of AVP and CRH receptors (AVPr1b, CRHR1, and CRHR2) in the pituitary gland.
  
  
  RESULTS
  The expression of depressive-like behavior in OB animals was reversed by treatment with both antidepressants. Surprisingly, OB-saline mice exhibited increased AVP and ACTH plasma levels, with no alterations in CRH levels when compared to sham mice. Chronic fluoxetine or venlafaxine reversed these effects. In addition, a significant increase only in AVPr1b gene expression was found in OB-saline.
  
  
  CONCLUSIONS
  The antidepressant therapy used seems to be more likely related to a reduced activation of AVP rather than CRH receptors, since a positive correlation between AVP levels and depressive-like behavior was observed in OB animals. Furthermore, a full restoration of depressive behavior was observed in OB-fluoxetine- or venlafaxine-treated mice only when AVP was centrally administered but not CRH.
authors.affiliation: Instituto de Fisiología, Instituto de Investigaciones en Ciencias de la Salud (INICSA, UNC-CONICET), Facultad de Ciencias Médicas, CONICET and Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Poretti
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, SE 75124, Sweden.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Sawant
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, SE 75124, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Rask-Andersen
authors.affiliation: Instituto de Fisiología, Instituto de Investigaciones en Ciencias de la Salud (INICSA, UNC-CONICET), Facultad de Ciencias Médicas, CONICET and Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Marta Fiol
authors.initials: MF
authors.lastname: de Cuneo
authors.affiliation: Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, SE 75124, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
authors.affiliation: Departamento de Farmacología, Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. mfperez@fcq.unc.edu.ar.
authors.forename: Mariela F
authors.initials: MF
authors.lastname: Perez
authors.affiliation: Instituto de Fisiología, Instituto de Investigaciones en Ciencias de la Salud (INICSA, UNC-CONICET), Facultad de Ciencias Médicas, CONICET and Universidad Nacional de Córdoba, Córdoba, Argentina. vcarlini@live.com.ar.
authors.forename: Valeria Paola
authors.initials: VP
authors.lastname: Carlini
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001127:Arginine Vasopressin / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000601:surgery; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000069470:Venlafaxine Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D018019:Receptors, Corticotropin-Releasing Hormone; D017483:Receptors, Vasopressin; D005473:Fluoxetine; D001127:Arginine Vasopressin; D000069470:Venlafaxine Hydrochloride; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone
keywords: AVPr1b; CRHR1; Corticotropin releasing hormone; Depressive behavior; Fluoxetine; Vasopressin; Venlafaxine