Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues

Abstract

Recent investigations have focused on the mitochondrion as a direct drug target in the treatment of metabolic diseases (obesity, metabolic syndrome). Relatively few studies, however, have explicitly investigated whether drug therapies aimed at changing behavior by altering central nervous system (CNS) function affect mitochondrial bioenergetics, and none has explored their effect during early neonatal development. The present study was designed to evaluate the effects of chronic treatment of newborn male rats with the selective serotonin reuptake inhibitor fluoxetine on the mitochondrial bioenergetics of the hypothalamus and skeletal muscle during the critical nursing period of development. Male Wistar rat pups received either fluoxetine (Fx group) or vehicle solution (Ct group) from the day of birth until 21 days of age. At 60 days of age, mitochondrial bioenergetics were evaluated. The Fx group showed increased oxygen consumption in several different respiratory states and reduced production of reactive oxygen species, but there was no change in mitochondrial permeability transition pore opening or oxidative stress in either the hypothalamus or skeletal muscle. We observed an increase in glutathione S-transferase activity only in the hypothalamus of the Fx group. Taken together, our results suggest that chronic exposure to fluoxetine during the nursing phase of early rat development results in a positive modulation of mitochondrial respiration in the hypothalamus and skeletal muscle that persists into adulthood. Such long-lasting alterations in mitochondrial activity in the CNS, especially in areas regulating appetite, may contribute to permanent changes in energy balance in treated animals.

Serotonin modulation in neonatal age does not impair cardiovascular physiology in adult female rats: Hemodynamics and oxidative stress analysis

“…In order to avoid any possible influence of the circadian rhythm on the measurements, all Fx and vehicle injections were administered between 7:00 and 8:00 AM. All surgical procedures and experiments were performed with the approval of the Animal Care Committee of the Federal University of Pernambuco, Brazil, under the process number 23,076.026644/2010-20 [17][18][19].…”

“…The treatments were applied from the 1st to the 21st postnatal day (i.e., during the suckling period) [17][18][19].…”

“…The CS activity was measured by assessing the rate of change in absorbance at 412 nm over 3 min (30-s intervals) [18].…”

Fluoxetine induces lean phenotype in rat by increasing the brown/white adipose tissue ratio and UCP1 expression

“…All male neonates received a subcutaneous fluoxetine (10 mg/kg, dissolved in saline solution, 10 ml/kg, bw; Fx group) or vehicle (NaCl 0.9 %, 10 ml/kg, bw; control-Ct group) injection once daily from the 1st to the 21st postnatal day (i.e., during the suckling period) as our previous studies (da da Silva et al 2015). To avoid a possible influence of the circadian rhythm in these studies, injections were always administered between 7:00 and 8:00 a.m. (Sanchez et al 2008;da Silva et al 2014).…”

Can fish oil supplementation and physical training improve oxidative metabolism in aged rat hearts?

“…For citrate synthase activity, 100 μg of protein was incubated in a reaction mixture containing (in mM) 100 Tris-HCl (pH 8.2), 1 MgCl 2 , 1 EDTA, 0.2 5,5-dithio-bis(2-nitrobenzoic acid) (DTNB) (ε = 13.6 μmol·ml −1 cm −1 ), 3 acetyl-CoA, and 5 oxaloacetate. The citrate synthase activity was measured by assessing the rate of change in absorbance at 412 nm over 3 min (30-s intervals) [36].…”