Samira S Valvassori

Publications (64)172.57 Total impact

• Article: Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

  Cinara L Gonçalves, Gislaine T Rezin, Gabriela K Ferreira, Isabela C Jeremias, Mariane R Cardoso, Samira S Valvassori, Bruna J P Munhoz, Gabriela D Borges, Bruno N Bristot, Daniela D Leffa, Vanessa M Andrade, João Quevedo, Emilio L Streck
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  ABSTRACT: Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage.
  Molecular and Cellular Biochemistry 05/2013; · 2.06 Impact Factor
• Article: Biological mechanisms underlying neuroprogression in bipolar disorder.

  Josiane Budni, Samira S Valvassori, João Quevedo
  Revista Brasileira de Psiquiatria 03/2013; 35(1):1-2. · 1.20 Impact Factor
• Article: Effects of sodium butyrate on oxidative stress and behavioral changes induced by administration of d-AMPH.

  Amanda V Steckert, Samira S Valvassori, Roger B Varela, Francielle Mina, Wilson R Resende, Daniela V Bavaresco, Felipe Ornell, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: Several evidences have demonstrated that oxidative stress has a central role in bipolar disorder (BD). Recently, studies have been suggested histone deacetylases (HDAC) as a possible target for new medications in treatment of mood disorders. In this study, we investigated the effects of sodium butyrate (SB, a histone deacetilase inhibitor) on oxidative stress in rats submitted to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for 14days, and then, between days 8 and 14, rats were treated with SB or Sal. Locomotor activity and risk-taking behavior were assessed by open-field test and oxidative stress was measured in prefrontal cortex, amygdala, hippocampus and striatum. The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment. The present study reinforces the need for more studies of HDAC inhibitors as possible target for new medications in treatment for BD.
  Neurochemistry International 02/2013; · 2.86 Impact Factor
• Article: Evaluation of acetylcholinesterase in an animal model of mania induced by d-amphetamine.

  Roger B Varela, Samira S Valvassori, Jéssica Lopes-Borges, Daiane B Fraga, Wilson R Resende, Camila O Arent, Alexandra I Zugno, João Quevedo
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  ABSTRACT: The present study aims to investigate the effects of mood stabilizers, lithium (Li) and valproate (VPA), on acetylcholinesterase (AChE) activity in the brains of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first given d-AMPH or saline (Sal) for 14 days. Between days 8 and 14, the rats were treated with Li, VPA, or Sal. In the prevention treatment, rats were pretreated with Li, VPA, or Sal. AChE activity was measured in the brain structures (prefrontal cortex, hippocampus, and striatum). Li, alone in reversion and prevention treatments, increased AChE activity in the brains of rats. VPA, alone in prevention treatment, increased AChE activity in all brain regions evaluated; in the reversion, only in the prefrontal. However, d-AMPH decreased activity of AChE in the striatum of rats in both the reversion and prevention treatments. VPA was able to revert and prevent this AChE activity alteration in the rat striatum. Our findings further support the notion that the mechanisms of mood stabilizers also involves changes in the AChE activity, thus reinforcing the need for more studies to better characterize the role of acetylcholine in bipolar disorder.
  Psychiatry research. 12/2012;
• Article: Folic acid prevents depressive-like behavior and hippocampal antioxidant imbalance induced by restraint stress in mice.

  Josiane Budni, Andréa Dias Zomkowski, Daiane Engel, Danúbia Bonfanti Santos, Alessandra Antunes Dos Santos, Morgana Moretti, Samira S Valvassori, Felipe Ornell, João Quevedo, Marcelo Farina, Ana Lúcia S Rodrigues
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  ABSTRACT: Experimental and epidemiological studies have shown the close relationship between stressful events, depression, and cognitive impairment. Folic acid has been reported to present antidepressant-like effects in both experimental and clinical approaches. However, the mechanisms mediating such effects are not understood. In the present study, we evaluated if folic acid administration to mice could protect against restraint stress-induced depressive-like behavior and cognitive deficit. Considering that oxidative stress has been pointed as a key event involved with depressive disorders, cerebrocortical and hippocampal oxidative stress-related parameters, such as the activities of antioxidant enzymes (mainly those related to the hydroperoxide-detoxifying system) and markers of lipid peroxidation, were also investigated. Restraint stress induced depressive-like behavior in the forced swimming test and memory impairment in the object recognition test, without altering locomotor activity of mice. Folic acid (50mg/kg, p.o.) was able to prevent the stress-induced increase on immobility time in the forced swimming test, but did not prevent memory impairment. Moreover, restraint stress increased thiobarbituric acid reactive substances levels, and catalase, glutathione peroxidase and glutathione reductase activities in the cerebral cortex and hippocampus, and superoxide dismutase activity in the hippocampus. Folic acid treatment restored the activity of the antioxidant enzymes and reduced lipid peroxidation in the hippocampus. Glutathione, a non-enzymatic antioxidant, was not altered by stress and/or folic acid administration. Together, the results of the present work reinforce the notion that folic acid displays a specific antidepressant profile in the restraint stress paradigm that may be at least partly due to its antioxidant role.
  Experimental Neurology 11/2012; · 4.70 Impact Factor
• Article: Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania.

  Kelen Cechinel-Recco, Samira S Valvassori, Roger B Varela, Wilson R Resende, Camila O Arent, Marcelo F Vitto, Gabrielle Luz, Claudio T de Souza, João Quevedo
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  ABSTRACT: Lithium (Li) is the main mood stabilizer and acts on multiple biochemical targets, leading to neuronal plasticity. Several clinical studies have shown that tamoxifen (TMX) - a protein kinase C (PKC) inhibitor - has been effective in treating acute mania. The present study aims to evaluate the effects of TMX on biochemical targets of Li, such as glycogen synthase kinase-3β (GSK-3β), PKC, PKA, CREB, BDNF and NGF, in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were treated with d-AMPH (2mg/kg, once a day) or saline (Sal; NaCl 0.9%, w/v), Li (47.5 mg/kg, intraperitoneally (i.p.), twice a day) or TMX (1 mg/kg i.p., twice a day) or Sal in protocols of reversion and prevention treatment. Locomotor behavior was assessed using the open-field task, and protein levels were measured by immunoblot. Li and TMX reversed and prevented d-AMPH-induced hyperactivity. Western blot showed that d-AMPH significantly increased GSK-3 and PKC levels, and decreased pGSK-3, PKA, NGF, BDNF and CREB levels in the structures analyzed. Li and TMX were able to prevent and reverse these changes induced by d-AMPH in most structures evaluated. The present study demonstrated that the PKC inhibitor modulates the alterations in the behavior, neurotrophic and apoptosis pathway induced by d-AMPH, reinforcing the need for more studies of PKC as a possible target for treatment of bipolar disorder.
  Journal of Psychopharmacology 10/2012; · 3.04 Impact Factor
• Article: Behavioral changes and brain energy metabolism dysfunction in rats treated with methamphetamine or dextroamphetamine.

  Gustavo Feier, Samira S Valvassori, Jéssica Lopes-Borges, Roger B Varela, Daniela V Bavaresco, Giselli Scaini, Meline O Morais, Monica L Andersen, Emilio L Streck, João Quevedo
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  ABSTRACT: Studies have demonstrated that AMPHs produce long-term damage to the brain dopaminergic, serotoninergic and glutamatergic regions. Prefrontal cortex, amygdala, hippocampus and striatum appear to be involved in the toxicity and behavioral changes induced by AMPHs. A single dose of AMPH causes mitochondrial dysfunction and oxidative stress in rat brain. The goal of the present study was thus to investigate the potency of two amphetamines, dextroamphetamine (d-AMPH) and methamphetamine (m-AMPH), on the behavior and energetic dysfunction in the brain of rats. d-AMPH and m-AMPH increased the crossing and rearing behaviors. The numbers of visits to the center were increased by d-AMPH and m-AMPH only at 2mg/kg. Likewise, at a high dose (2mg/kg), the injection of m-AMPH increased the amount of sniffing. The AMPHs significantly decreased the activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase) and mitochondrial respiratory chain complexes (I-IV); nevertheless, this effect varied depending on the brain region evaluated. In summary, this study demonstrated that at high doses, m-AMPH, increased stereotyped (sniffing) behavior in rats, but d-AMPH did not. However, this study shows that d-AMPH and m-AMPH seem to have similar effects on the brains energetic metabolism.
  Neuroscience Letters 09/2012; · 2.11 Impact Factor
• Article: Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine.

  Gustavo Feier, Samira S Valvassori, Roger B Varela, Wilson R Resende, Daniela V Bavaresco, Meline O Morais, Lis M Mello-Santos, Monica L Andersen, Emilio L Streck, João Quevedo
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  ABSTRACT: Studies have shown alterations in mitochondrial complexes of bipolar disorder (BD) patients. However, changes in the Krebs cycle enzymes have been little studied. The animal model of mania induced by amphetamine has been widely used for the study of bipolar mania. The aim of this study is to assess behavioral and energy metabolism changes in an animal model of mania induced by methamphetamine (m-AMPH). Wistar rats were first given m-AMPH or saline for 14days, and then, between days 8 and 14, rats were treated with lithium (Li), valproate (VPA), or saline (Sal). Locomotor behavior was assessed using the open-field task and activities of Krebs cycle enzymes (citrate synthase and succinate dehydrogenase), mitochondrial respiratory chain complexes (I, II, III, and IV), and creatine kinase measured in the brain structures (prefrontal, amygdala, hippocampus, and striatum). Li and VPA reversed m-AMPH-induced hyperactivity. The administration of m-AMPH inhibited the activities of Krebs cycle enzymes and complexes of the mitochondrial respiratory chain in all analyzed structures. Li and VPA reversed m-AMPH-induced energetic metabolism dysfunction; however, the effects of Li and VPA were dependent on the brain region analyzed. From the results obtained in this study, we suggested that the decreased Krebs cycle enzymes activity induced by m-AMPH may be inhibiting mitochondrial respiratory chain complexes. Therefore, changes in the Krebs cycle enzymes may also be involved in BD.
  Pharmacology Biochemistry and Behavior 09/2012; · 2.53 Impact Factor
• Article: Long-term decrease in immediate early gene expression after electroconvulsive seizures.

  Julien Braga Calais, Samira S Valvassori, Wilson R Resende, Gustavo Feier, Maria Carolina Pedro Athié, Sidarta Ribeiro, Wagner Farid Gattaz, João Quevedo, Elida Benquique Ojopi
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  ABSTRACT: Electroconvulsive therapy (ECT) is a well-established psychiatric treatment for severe depression. Despite its clinical utility, post-ECT memory deficits are a common side effect. Neuronal plasticity and memory consolidation are intimately related to the expression of immediate early genes (IEG), such as Egr1, Fos and Arc. Changes in IEG activation have been postulated to underlie long-term neuronal adaptations following electroconvulsive seizures (ECS), an animal model of ECT. To test this hypothesis, we used real-time PCR to examine the effect of acute and chronic ECS (8 sessions, one every other day) on the long-term (>24 h) expression of IEG Egr1, Fos and Arc in the hippocampus, a brain region implicated both in the pathophysiology of depression as well as in memory function. We observed a transient increase in Egr1 and Fos expression immediately after ECS, followed by a long-term decrease of IEG levels after both acute and chronic ECS. A separate group of animals, submitted to the same chronic ECS protocol and then subjected to open field or passive avoidance tasks, confirmed robust memory deficits 2 weeks after the last chronic ECS. The possible role of IEG downregulation on long-term learning deficits observed following ECS are discussed.
  Acta Neurovegetativa 08/2012; · 2.73 Impact Factor
• Article: Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

  Gislaine T Rezin, Giselli Scaini, Gabriela K Ferreira, Mariane R Cardoso, Cinara L Gonçalves, Larissa S Constantino, Pedro F Deroza, Fernando V Ghedim, Samira S Valvassori, Wilson R Resende, João Quevedo, Alexandra I Zugno, Emilio L Streck
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  ABSTRACT: Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.
  Metabolic Brain Disease 07/2012; · 2.20 Impact Factor
• Article: Evaluation of the brain-derived neurotrophic factor, nerve growth factor and memory in adult rats survivors of the neonatal meningitis by Streptococcus agalactiae.

  Tatiana Barichello, Joelson C Lemos, Jaqueline S Generoso, Mirelle M Carradore, Ana Paula Moreira, Allan Collodel, Jessiele R Zanatta, Samira S Valvassori, João Quevedo
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  ABSTRACT: Streptococcus agalactiae (GBS) is a major cause of severe morbidity and mortality in neonates and young infants, causing sepsis, pneumonia and meningitis. The survivors from this meningitis can suffer serious long-term neurological consequences, such as, seizures, hearing loss, learning and memory impairments. Neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) control the neuronal cell death during the brain development and play an important role in neuronal differentiation, survival and growth of neurons. Neonate Wistar rats, received either 10μL of sterile saline as a placebo or an equivalent volume of GBS suspension at a concentration of 1×10(6)cfu/mL. Sixty days after induction of meningitis, the animals underwent behavioral tests, after were killed and the hippocampus and cortex were retired for analyze of the BDNF and NGF levels. In the open-field demonstrated no difference in motor, exploratory activity and habituation memory between the groups. The step-down inhibitory avoidance, when we evaluated the long-term memory at 24h after training session, we found that the meningitis group had a decrease in aversive memory when compared with the long-term memory test of the sham group. BDNF levels decreased in hippocampus and cortex; however the NGF levels decreased only in hippocampus. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to GBS meningitis.
  Brain research bulletin 06/2012; · 2.18 Impact Factor
• Article: Effects of lithium and valproate on oxidative stress and behavioral changes induced by administration of m-AMPH.

  Dayane D da-Rosa, Samira S Valvassori, Amanda V Steckert, Felipe Ornell, Camila L Ferreira, Jéssica Lopes-Borges, Roger B Varela, Felipe Dal-Pizzol, Monica L Andersen, João Quevedo
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  ABSTRACT: In the last years our research group has studied and validated the animal model of mania induced by dextroamphetamine (d-AMPH). Considering the lack of animal models of mania reported in the literature; this study evaluated the possibilities to validate the animal model induced by methamphetamine (m-AMPH). Then, we evaluated the effects of lithium (Li), valproate (VPA) on the behavior and parameters of oxidative damage in rat brain after administration of m-AMPH. In the prevention treatment, Wistar rats were pretreated with Li, VPA or saline (Sal) for 14days, and then, between days 8 and 14, rats were treated with m-AMPH (1, 0.5 or 0.25mg/kg) or Sal. In the reversal treatment, rats were first given m-AMPH (0.25mg/kg) or Sal. Locomotor behavior was assessed using the open-field task and parameters of oxidative damage were measured in brain structures. Our results show that the hyperactivity was prevented and reverted by Li and VPA only when m-AMPH was administered in the dose of 0.25mg/kg. In addition, the m-AMPH in all doses administrated induced oxidative damage in both structures tested in two models. Li and VPA reversed and prevented this impairment, however in a way dependent of cerebral area, the dose of m-AMPH and technique.
  Psychiatry Research 03/2012; · 2.52 Impact Factor
• Article: Behavioral and neurochemical effects of sodium butyrate in an animal model of mania.

  Morgana Moretti, Samira S Valvassori, Roger B Varela, Camila L Ferreira, Natalia Rochi, Joana Benedet, Giselli Scaini, Flávio Kapczinski, Emilio L Streck, Alexandra I Zugno, João Quevedo
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  ABSTRACT: The present study investigated the effect of the histone deacetylase inhibitor, sodium butyrate (SB), on locomotor behavior and on mitochondrial respiratory-chain complexes activity in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first treated with d-AMPH or saline (Sal) for 14 days. Thereafter, between days 8 and 14, rats were administered SB or Sal. In the prevention treatment, rats were treated with SB or Sal for 14 days and received d-AMPH or Sal between days 8 and 14. The d-AMPH treatment increased locomotor behavior in Sal-treated rats under reversion and prevention treatment, and SB reversed and prevented d-AMPH-related hyperactivity. Moreover, d-AMPH decreased the activity of mitochondrial respiratory-chain complexes in Sal-treated rats in the prefrontal cortex, hippocampus, striatum, and amygdala in both experiments, and SB was able to reverse and prevent this impairment. The present study suggests that the mechanism of action of SB involves induction of mitochondrial function in parallel with behavioral changes, reinforcing the need for more studies on histone deacetylase inhibitors as a possible target for new medications for bipolar disorder treatment.
  Behavioural pharmacology 12/2011; 22(8):766-72. · 2.85 Impact Factor
• Article: Differences between dextroamphetamine and methamphetamine: behavioral changes and oxidative damage in brain of Wistar rats.

  Dayane D da-Rosa, Samira S Valvassori, Amanda V Steckert, Camila O Arent, Camila L Ferreira, Jéssica Lopes-Borges, Roger B Varela, Edemilson Mariot, Felipe Dal-Pizzol, Monica L Andersen, João Quevedo
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  ABSTRACT: In this study methamphetamine (m-AMPH) and dextroamphetamine (d-AMPH) were compared to determine the potency of the two drugs on behavior and oxidative damage in brain of rats. Male adult Wistar rats were given single (acute administration) or repeated (chronic administration, 14 days) intraperitoneal injections of saline (0.9% NaCl), d-AMPH (2 mg/kg) or m-AMPH (0.25, 0.5, 1 or 2 mg/kg). Locomotor activity was evaluated in open-field apparatus 2 h after the last drug injection. Additionally, thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the prefrontal cortex, amygdala, hippocampus and striatum. In both experiments, d-AMPH and m-AMPH (all doses administered) increased the locomotor activity of animals, meantime, no significant difference between d-AMPH and m-AMPH was observed. d-AMPH and m-AMPH increased lipid and protein damage, but m-AMPH was more potent than d-AMPH, however, this effect varies depending on the brain region and the experimental protocol. The results of this study show that d-AMPH and m-AMPH have similar behavioral effects, which previous studies had already reported. On the other hand, this study demonstrated that the m-AMPH induces oxidative damage greater than d-AMPH, showing neurochemical differences previously unknown.
  Acta Neurovegetativa 08/2011; 119(1):31-8. · 2.73 Impact Factor
• Article: Brain energy metabolism is activated after acute and chronic administration of fenproporex in young rats.

  Gislaine T Rezin, Isabela C Jeremias, Gabriela K Ferreira, Mariane R Cardoso, Meline O S Morais, Lara M Gomes, Otaviana B Martinello, Samira S Valvassori, João Quevedo, Emilio L Streck
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  ABSTRACT: Obesity is a chronic disease of multiple etiologies, including genetic, metabolic, environmental, social, and other factors. Pharmaceutical strategies in the treatment of obesity include drugs that regulate food intake, thermo genesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine. Studies suggest that amphetamine induces neurotoxicity through generation of free radicals and mitochondrial apoptotic pathway by cytochrome c release, accompanied by a decrease of mitochondrial membrane potential. Mitochondria are intracellular organelles that play a crucial role in ATP production. Thus, in the present study we evaluated the activities of some enzymes of Krebs cycle, mitochondrial respiratory chain complexes and creatine kinase in the brain of young rats submitted to acute and chronic administration of fenproporex. In the acute administration, the animals received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or tween. In the chronic administration, the animals received a single injection daily for 14 days of fenproporex (6.25, 12.5 or 25 mg/Kg i.p.). Two hours after the last injection, the rats were sacrificed by decapitation and the brain was removed for evaluation of biochemical parameters. Our results showed that the activities of citrate synthase, malate dehydrogenase and succinate dehydrogenase were increased by acute and chronic administration of fenproporex. Complexes I, II, II-III and IV and creatine kinase activities were also increased after acute and chronic administration of the drug. Our results are consistent with others reports that showed that some psychostimulant drugs increased brain energy metabolism in young rats.
  International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 06/2011; 29(8):937-42. · 2.03 Impact Factor
• Article: Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases.

  Gustavo Feier, Samira S Valvassori, Gislaine T Rezin, Márcio Búrigo, Emilio L Streck, Flávio Kapczinski, João Quevedo
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  ABSTRACT: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic), and healthy volunteers. Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring < 8 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS); manic-scoring < 7 on the HDRS and > 7 on the YMRS; depressive-scoring > 7 on the HDRS and < 7 on the YMRS. Patients in mixed phases were excluded. Blood samples were collected from all participants. Creatine kinase levels were higher in the manic patients than in the controls. However, we observed no significant difference between euthymic and depressive patients in terms of the creatine kinase level. Our results suggest that the clinical differences among the depressive, manic, and euthymic phases of bipolar disorder are paralleled by contrasting levels of creatine kinase. However, further studies are needed in order to understand the state-dependent differences observed in serum creatine kinase activity.
  Revista Brasileira de Psiquiatria 06/2011; 33(2):171-5. · 1.20 Impact Factor
• Article: Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain

  Tiago P. Freitas, Gislaine T. Rezin, Daiane B. Fraga, Morgana Moretti, Julia S. Vieira, Lara M. Gomes, Lislaine S. Borges, Samira S. Valvassori, João Quevedo, Emilio L. Streck
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  ABSTRACT: Freitas TP, Rezin GT, Fraga DB, Moretti M, Vieira JS, Gomes LM, Borges LS, Valvassori SS, Quevedo J, Streck EL. Mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Objectives: Bipolar disorder (BD) is a mental illness associated with higher rates of suicide. The present study aims to investigate the brain mitochondrial respiratory chain activity in an animal model of mania induced by ouabain.Methods: Adult male Wistar rats received a single intracerebroventricular administration of ouabain (10−3 and 10−2 M) or vehicle. Locomotor activity was measured using the open field test. Mitochondrial respiratory chain activity was measured in the brain of rats 1 h and 7 days after ouabain administration.Results: Our results showed that spontaneous locomotion was increased 1 h and 7 days after ouabain administration. Complexes I, III and IV activities were increased in the prefrontal cortex, hippocampus and striatum immediately after the administration of ouabain, at the concentration of 10−3 and 10−2 M. Moreover, complex II activity was increased only in the prefrontal cortex at the concentration of 10−2 M. On the other hand, no significant alterations were observed in complex I activity 7 days after ouabain administration. However, an increase in complexes II, III and IV activities was observed only in the prefrontal cortex at the concentration of 10−2 M.Conclusion: Our findings suggest an increase in the activities of mitochondrial respiratory chain in this model of mania. A possible explanation is that these findings occur as a rebound effect trying to compensate for a decrease of ATP deprivation in BD. The present findings suggest that this model may present good face validity and a limitation in construct validity.
  Acta Neuropsychiatrica 03/2011; 23(3):106 - 111. · 0.58 Impact Factor
• Article: Neuroanatomical profile of antimaniac effects of histone deacetylases inhibitors.

  Camila O Arent, Samira S Valvassori, Gabriel R Fries, Laura Stertz, Camila L Ferreira, Jéssica Lopes-Borges, Edemilson Mariot, Roger B Varela, Felipe Ornell, Flávio Kapczinski, Monica L Andersen, João Quevedo
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  ABSTRACT: An increasing number of studies have evaluated the potential therapeutic relevance of histone deacetylases (HDAC) inhibitors in mood disorder including bipolar disorder (BD). It has been suggested that the anterior limbic, which controls impulsivity and psychosis, is dysfunctional in BD. The present studies aims to evaluate the effects of microinjection of HDAC inhibitors in the ventricle, amygdala, striatum, prefrontal, and hippocampus on m-amphetamine-induced manic-like behavior in rats. Rats were given a single intracerebral (in the ventricle, amygdala, striatum, prefrontal, or hippocampus) injection of artificial cerebrospinal fluid, sodium butyrate (SB), or valproate (VPA) followed by an intraperitoneal injection of saline or m-AMPH 2 h before the open-field task. The activity of HDAC was evaluated in amygdala, striatum, prefrontal, and hippocampus of animals. The microinjection of SB and VPA in the ventricle, amygdala, striatum, and prefrontal, but not in hippocampus blocked the hyperactivity induced by m-AMPH. In addition, SB and VPA inhibited the HDAC activity; however, this effect varied depending on the experimental procedure and the brain structure evaluated. Our results suggest that the antimanic effects of SB and VPA, HDAC inhibitors, are related to the amygdala, striatum, and prefrontal, but not the hippocampus. More studies are needed to clarify the therapeutic effects of the HDAC inhibitor in BD and thereby develop new drugs.
  Molecular Neurobiology 03/2011; 43(3):207-14. · 5.74 Impact Factor
• Article: Evaluation of light/dark cycle in anxiety- and depressive-like behaviors after regular treatment with methylphenidate hydrochloride in rats of different ages.

  Karin M Gomes, Renan P Souza, Cecília G Inácio, Samira S Valvassori, Gislaine Z Réus, Márcio R Martins, Clarissa M Comim, João Quevedo
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  ABSTRACT: Methylphenidate hydrochloride is the most widely used medication for treatment and management of attention-deficit hyperactivity disorder. However, the chronic effects of methylphenidate hydrochloride on anxiety- and depressive-like rat behaviors remain poorly investigated. In this context, the present study evaluated the effects of treatment with methylphenidate hydrochloride on anxiety- and depressive-like behaviors using young and adult rats during the light and the dark cycle. Male Wistar rats (25 or 60 days old) received a once-daily (in either the light or dark cycle) methylphenidate hydrochloride (2mg/kg) or saline intraperitoneal injection for 28 days. We performed elevated plus maze and forced swimming test two hours after the last injection. The light/dark cycle was a significant factor in the anxiety-like behaviors; however, no significant interaction between all three factors (cycle, age and methylphenidate hydrochloride) was found. Nevertheless, we observed a nominally significant interaction between the light/ dark cycle and age in the forced swimming test. Our results have shown that age and the light/dark cycle are more significant modulators of anxiety- and depressive-like behaviors than methylphenidate hydrochloride treatment.
  Revista Brasileira de Psiquiatria 03/2011; 33(1):55-8. · 1.20 Impact Factor
• Article: Lithium and valproate modulate antioxidant enzymes and prevent ouabain-induced oxidative damage in an animal model of mania.

  Luciano K Jornada, Samira S Valvassori, Amanda V Steckert, Morgana Moretti, Francielle Mina, Camila L Ferreira, Camila O Arent, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: In this study, we assessed the oxidative stress parameters in rats submitted to an animal model of mania induced by ouabain (OUA), which included the use of lithium (Li) and valproate (VPA). Li and VPA treatment reversed and prevented the OUA-induced damage in these structures, however, this effect varies depending on the brain region and treatment regimen. Moreover, the activity of the antioxidant enzymes, namely, superoxide dismutase (SOD) and catalase (CAT) was found to be increased and decreased, respectively, in the brain of OUA-administered rats. Li and VPA modulated SOD and CAT activities in OUA-subjected rats in both experimental models. Our results support the notion that Li and VPA exert antioxidant-like properties in the brain of rats submitted to animal model of mania induced by ouabain.
  Journal of psychiatric research 02/2011; 45(2):162-8. · 3.72 Impact Factor