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Influence of lactational exposure to venlafaxine antidepressant: late repercussion on reproductive and behavioral parameters, in male rats

Grant number: 19/02902-8
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2019
Effective date (End): March 31, 2021
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Arielle Cristina Arena
Grantee:Suyane da Silva Moreira
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

The overall prevalence of postpartum depression is estimated at 100-150 cases per 1000 births, and one of the most indicated drugs for treatment is Venlafaxine, a Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). As serotonin plays a key role in brain development, studies have shown that prenatal exposure to SSRIs can alter the hypothalamic-pituitary-adrenal (HHA) and gonadal (HHG) axes and affect hormone-dependent processes, such as the process of hypothalamic sexual differentiation. Due to the importance of testosterone in the process of hypothalamic sexual differentiation, the use of antidepressants during gestation is of concern. Thus, the objective of this study was to evaluate the possible effects of venlafaxine on lactational exposure and its late repercussions on reproductive parameters in male rats. For this, lactating rats will be exposed to three doses of venlafaxine (7.5, 37.5 or 75 mg / kg), via gavage, from the 1th until the 20th day postpartum. After birth, male offspring will be evaluated through the following parameters: body weight determination, anogenital distance and ages of preputial separation and testicular descente, and play behavior. In adult life, these same animals will be investigated for: reproductive organ weights, sperm count, morphology and sperm motility, hormonal dosage, histopathological analysis of the testis, epididymis, pituitary and hypothalamus, Sertoli and Leydig cell counts, behavior sexual preference, and fertility testing. The present study, in addition to providing opportunities for the training of qualified human resources, could generate important information for the implementation of government public health policies aimed at greater control of the use of this medication class during pregnancy.