Research Report Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure Benício N. Frey a,b,c , Samira S. Valvassori d , Karin M. Gomes d , Márcio R. Martins d , Felipe Dal-Pizzol e , Flávio Kapczinski a,b , João Quevedo d, ⁎ a Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil b Bipolar Disorders Program, Hospital de Clínicas de Porto Alegre, 90035-003 Porto Alegre, RS, Brazil c MOOD-CNS Program, Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, TX 78229, USA d Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil e Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil ARTICLE INFO ABSTRACT Article history: Accepted 17 April 2006 Available online 30 May 2006 Previous studies have suggested that reactive oxygen species (ROS) production may play a role in the pathophysiology of many neuropsychiatric disorders, such as bipolar disorder (BD) and schizophrenia (SCZ). In addition, there is an emerging body of data indicating that BD and SCZ may be associated with mitochondrial dysfunction. We studied the effects of acute and chronic d-amphetamine on ROS production in submitochondrial particles of rat brain. Male Wistar rats were divided in two experimental groups: acute and chronic treatment. In the acute treatment, rats received one single IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline (control group). In the chronic treatment, rats received one daily IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline for 7 days. Locomotor activity was assessed with the open field task, and thiobarbituric acid reactive substances (TBARS) and superoxide production were measured in submitochondrial particles of the prefrontal cortex and hippocampus. Both acute and chronic amphetamine treatment increased locomotor behavior. Chronic amphetamine exposure induced a 3- to 6-fold increase of TBARS and a 1.5- to 2-fold increase of superoxide production in submitochondrial particles of prefrontal cortex and hippocampus (P < 0.05). No effects on superoxide or TBARS were observed with acute treatment. These findings suggest that amphetamine-induced mitochondrial ROS generation may be a useful model to investigate the hypothesis of altered brain energy metabolism associated with BD and SCZ. Further studies assessing the effects of mood stabilizers and antipsychotics in preventing mitochondrial oxidative stress are necessary. © 2006 Elsevier B.V. All rights reserved. Keywords: Amphetamine Animal model Bipolar disorder Oxidative stress Schizophrenia Submitochondrial particle Abbreviations: BD, bipolar disorder ETC, electron transport chain ROS, reactive oxygen species SCZ, schizophrenia SMP, submitochondrial particles TBARS, thiobarbituric acid reactive substances BRAIN RESEARCH 1097 (2006) 224 – 229 ⁎ Corresponding author. Fax: +55 48 3443 4827. E-mail address: quevedo1@terra.com.br (J. Quevedo). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.04.076 available at www.sciencedirect.com www.elsevier.com/locate/brainres