Role of Vasopressin and Corticotropin Releasing Hormone receptors in the Effects of Fluoxetine and Venlafaxine on the expression of depression-related behavior.

MARIA BELEN PORETTI; BIANCONI SANCIAGO; MATHIAS RASK-ANDERSEN; MARTA FIOL DE CUNEO; GRACIELA STUTZ; HELGI B. SCHIOTH; MARIELA FERNANDA PÉREZ; VALERIA PAOLA CARLINI

Mar del Plata

Congreso; LX Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC). Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2015

Sociedad Argentina de Fisiología (SAFIS).

Rationale: 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: 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 (mice with olfactory bulbectomy, OB) the effects of fluoxetine or venlafaxine (both 10 mg/kg/day) chronic administration in a depression-related behavior were evaluated in the tail suspension test, (TST). In these animals AVP,CRH and ACTH plasma levels were determined; participation of their receptors in the expression of depression related-behavior were evaluated; and gene expression of APV and CRH receptors (AVPr1b, CRHR1 and CRHR2) in the pituitary gland was measured.Results: The expression of the depressive-like behavior in OB animals was reversed by treatment with both antidepressants. Surprisingly, OB-saline mice exhibited increased AVP and ACTH (p < 0.05) 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 (p < 0.05). Conclusion: The antidepressant therapy used seems to be more likely related to a reduced activation of the AVP rather than CRH receptors, since a positive correlation between APV 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 APV was centrally administered but not CRH.