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

PORETTI, MARIA BELÉN; SAWANT, RAHUL; RASK-ANDERSEN, MATHIAS; FIOL DE CUNEO, MARTA; SCHIÖTH, HELGI; PÉREZ, MARIELA F; VALERIA P CARLINI

PSYCHOPHARMACOLOGY

SPRINGER

Lugar: Berlin; Año: 2015 vol. 233 p. 1077 - 1086

0033-3158

Rationale: In response to stress, corticotropin releasing hormone (CRH) andvasopressin (AVP) are released from the hypothalamus, activate their receptors(CRHR1, CRHR2 or AVPr1b), and synergistically act to induce adrenocorticotropichormone (ACTH) release from the anterior pituitary. Overstimulation of this system has been frequently associated with major depression states.Objective: to assess the role of AVP and CRH receptors in fluoxetine and venlafaxineeffects on the expression of depression-related behavior.Methods: In an animal model of depression (olfactory bulbectomy in mice, OB) weevaluated the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronicadministration 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 CRHreceptors (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.Conclusion: The antidepressant therapy used seems to be more likely related to areduced 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.