Serotonin transporter inhibition during neonatal period induces sex‐dependent effects on mitochondrial bioenergetics in the rat brainstem

• Published in: The European journal of neuroscience Vol. 48; no. 1; pp. 1620 - 1634
• Main Authors: Silva, Tercya Lucidi Araujo, Braz, Glauber Rudá Feitoza, Silva, Severina Cassia de Andrade, Pedroza, Anderson Apolônio da Silva, Freitas, Cristiane de Moura, Ferreira, Diorginis José Soares, da Silva, Aline Isabel, Lagranha, Claudia Jacques
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.07.2018
• Subjects: Antidepressants; Antioxidants; Bioenergetics; brain; Brain stem; Cardiovascular diseases; Fluoxetine; Lactation; Mitochondria; Neonates; oxidative phosphorylation; Oxidative stress; Raphe nuclei; Rodents; Serotonin; Serotonin transporter; Serotonin uptake inhibitors; UCP 2; UCP 2; fluoxetine; brain; oxidative phosphorylation
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.13971

The serotonin reuptake is mainly regulated by the serotonin transporters (SERTs), which are abundantly found in the raphe nuclei, located in the brainstem. Previous studies have shown that dysfunction in the SERT has been associated with several disorders, including depression and cardiovascular diseases. In this manuscript, we aimed to investigate how gender and the treatment with a serotonin selective reuptake inhibitor (SSRI) could affect mitochondrial bioenergetics and oxidative stress in the brainstem of male and female rats. Fluoxetine, our chosen SSRI, was used during the neonatal period (i.e., from postnatal Day 1 to postnatal Day 21—PND1 to PND21) in both male and female animals. Thereafter, experiments were conducted in adult rats (60 days old). Our results demonstrate that, during lactation, fluoxetine treatment modulates the mitochondrial bioenergetics in a sex‐dependent manner, such as improving male mitochondrial function and female antioxidant capacity. SSRI enhances mitochondrial function and oxidative balance in a gender‐dependent manner. Fluoxetine exerts additional antioxidant capacity in female rats. Neonatal SSRI treatment modulates phosphorylative capacity in adult male rats.