Reduced vasopressin receptors activation mediates the anti-depressant effects of fluoxetine and venlafaxine in bulbectomy model of depression.

RAHUL S SAWANT; HELGI B. SCHIOTH; MARIA BELEN PORETTI; MARTA FIOL DE CUNEO; VALERIA PAOLA CARLINI; MATHIAS RASK-ANDERSEN; PERÉZ MF

PSYCHOPHARMACOLOGY

SPRINGER

Lugar: Berlin; Año: 2016 vol. 233 p. 1077 - 1086

0033-3158

Rationale In response to stress, corticotropin releasing hormone(CRH) and vasopressin (AVP) are released from thehypothalamus, activate their receptors (CRHR1, CRHR2 orAVPr1b), and synergistically act to induce adrenocorticotropichormone (ACTH) release from the anterior pituitary.Overstimulation of this system has been frequently associatedwith major depression states.Objective The objective of the study is to assess the role ofAVP and CRH receptors in fluoxetine and venlafaxine effectson the expression of depression-related behavior.Methods In an animal model of depression (olfactorybulbectomy in mice, OB), we evaluated the effects offluoxetine or venlafaxine (both 10 mg/kg/day) chronic administrationon depression-related behavior in the tail suspensiontest. Plasma levels of AVP, CRH, and ACTH were determinedas well as participation of their receptors in the expression ofdepression related-behavior and gene expression of AVP andCRH receptors (AVPr1b, CRHR1, and CRHR2) in the pituitarygland.Results The expression of depressive-like behavior in OB animalswas reversed by treatment with both antidepressants.Surprisingly, OB-saline mice exhibited increased AVP andACTH plasma levels, with no alterations in CRH levels whencompared to sham mice. Chronic fluoxetine or venlafaxinereversed these effects. In addition, a significant increase onlyin AVPr1b gene expression was found in OB-saline.Conclusion The antidepressant therapy used seems to bemore likely related to a reduced activation of AVP rather thanCRH receptors, since a positive correlation between AVPlevels and depressive-like behavior was observed in OB animals.Furthermore, a full restoration of depressive behaviorwas observed in OB-fluoxetine- or venlafaxine-treated miceonly when AVP was centrally administered but not CRH.