Effects of fluoxetine withdrawal in the brainstem and hypothalamus of overnourished rats: Chronic modulation on oxidative stress levels

Abstract

Poor nutritional quality in the early stages of development is associated with neurological diseases in adulthood. Studies showed that obesity-induced oxidative stress contributes to the genesis of neurological diseases through dysregulation of the brainstem and hypothalamus. Fluoxetine (Fx) is an antidepressant member in the family of selective serotonin reuptake inhibitors (SSRI) that can induce positive effects by reducing oxidative damage in brain tissues. We aimed to evaluate the late effect of Fx in the brainstem and hypothalamus of overnourished rats during development. Male Wistar rats, after birth, were randomly divided into the normal-nourished group (N, n = 9) and the overnourished group (O, n = 3). On the 39th day of life, the groups were subdivided into normofed, and the overnourished group treated or not with fluoxetine (10 mg/kg daily) (NF, NV, OF, and OV). All groups were treated from the 39th to the 59th day of life, and within 90 days, the tissues were collected for oxidative stress analysis. Briefly, our results showed that Fx treatment induced a tissue-dependent long-lasting effect in overfed animals, increasing the enzymatic defense (i.e., CAT and GST activity) in the hypothalamus, but more intensive, increasing the non-enzymatic defense (i.e., Total Thiols and GSH levels) in the brainstem. Overall, our study suggests that serotonin modulation at the final stage of brain development causes a long-lasting impact on brain structures in overfed rats at a different mode.

Keywords: brainstem; fluoxetine; hypothalamus; overnutrition; oxidative stress.