FLUOXETINE AND VENLAFAXINE EFFECT ON RECEPTORS EXPRESSION INVOLVED IN DEPERESSION IN PITUITARY GLAND

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

Mendoza

Congreso; 2da Reunión Conjunta de Sociedades de Biología de la República Argentina; 2011

Sociedad de Biología de Córdoba

Depression is biochemical imbalance, mainly of neuropeptides and neural hormones leading to change in mood. Apart from many affected brain regions, depression is mainly characterized by increased hypothalamic-pituitary-adrenal (HPA) axis activity. Many behavioral, endocrine and pharmacological similarities have been observed between olfactory bulbectomized rats and patients with depression. Chronic, but not acute, treatment of several classes of antidepressants is effective in treating depression, despite their side effects and withdrawal symptoms. Many antidepressants have been observed to reduce elevated levels of cortisol, the major stress hormone, through a decreased HPA activity. Corticotrophin releasing hormone (CRH) and vasopressin (VP) play important roles in mediating the ACTH release through their receptors CRHR1 and AVPr1b respectively. The purpose of the present study was to investigate, in an experimental model, the fluoxetine and venlafaxin effects on the expression of these receptors in pituitary gland. Adult male Albino?s Swiss mice were divided in two groups: sham operated (SO) and olfactory bulbectomy (OB). Both group were divided and orally treated, during 28 days with saline flouxetine (10 mg/Kg/day) or venlafaxine (10 mg/Kg/day). The last day of treatment, the tail suspension test was applied in order to determine a depressive behavior and then, the mice were sacrificed and their pituitary were collected by dissection, in order to study, using real time PCR, the mRNA CRHR1 and AVPr1b expression. After fluoxetine treatment CRHR1 (F = 8.415, p = 0.0009, n = 5) and AVPR1b (F = 3.343, p = 0.046, n= 5) expression increased in SO mice whereas in OB mice only CRHR1 (F= 8.415, p = 0.0009, n = 5) expression was increased. Both animals treated with fluoxetine or venlafaxine showed antidepressant behaviour, evidence by reduction in the immobility time in the tail suspension test (F = 8.57, p ≤0.05, n = 15) in SO and BO mice. Increased expression of CRHR1 and AVPR1b in pituitary after fluoxetine treatment could be a compensatory mechanism for decreased CRH and VP in the hypothalamus.