Effect of fluoxetine treatment on mitochondrial bioenergetics in central and peripheral rat tissues.
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.
Programa de Pós-Graduação em Nutrição, Departamento de Nutrição da Universidade Federal de Pernambuco, Recife, Brazil., Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, CAV-Federal University of Pernambuco, Brazil.
Aline Isabel
AI
da Silva
Glauber Ruda Feitoza
GR
Braz
Reginaldo
R
Silva-Filho
Anderson Apolonio
AA
Pedroza
Diorginis Soares
DS
Ferreira
Raul
R
Manhães de Castro
Claudia
C
Lagranha
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D005473:Fluoxetine; D013482:Superoxide Dismutase; D005982:Glutathione Transferase
central nervous system; energy balance; mitochondrial metabolism; muscle squelettique; métabolisme mitochondrial; skeletal muscle; système nerveux central; équilibre énergétique