Samira S Valvassori

Publications (64)172.57 Total impact

• Article: Tamoxifen effects on respiratory chain complexes and creatine kinase activities in an animal model of mania.

  Morgana Moretti, Samira S Valvassori, Amanda V Steckert, Natalia Rochi, Joana Benedet, Giselli Scaini, Flávio Kapczinski, Emilio L Streck, Alexandra I Zugno, João Quevedo
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  ABSTRACT: The present study aimed to investigate the effects of tamoxifen (TMX) on locomotor behavior and on the activities of mitochondrial respiratory chain complexes and creatine kinase (CK) in the brain of rats subjected to an animal model of mania induced by d-amphetamine (D-AMPH)-reversion and prevention protocols. The D-AMPH administration increased locomotor activity in saline-treated rats under prevention and reversion treatment; furthermore, there was evident reduction in the locomotion in the D-amphetamine group treated with TMX. D-AMPH significantly decreased the activity of mitochondrial respiratory chain complexes in saline-treated rats in prefrontal cortex, hippocampus, striatum and amygdala in both prevention and reversion treatment. Depending on the cerebral area and evaluated complex, TMX was able to prevent and reverse this impairment. A decrease in CK activity was also verified in the brain of rats when D-AMPH was administrated in both experiments; the administration of TMX reversed but not prevented the decrease in CK activity induced by D-AMPH. The present study demonstrated that TMX reversed and prevented the alterations in behavioral and energy metabolism induced by D-AMPH (alterations were also observed in bipolar disorder), reinforcing the need for more studies about inhibitors of PKC as possible targets for new medications in the treatment of bipolar disorder.
  Pharmacology Biochemistry and Behavior 01/2011; 98(2):304-10. · 2.53 Impact Factor
• Article: Effect of acute and chronic administration of methylphenidate on mitochondrial respiratory chain in the brain of young rats.

  Ana O Fagundes, Maira R Aguiar, Claudia S Aguiar, Giselli Scaini, Monique U Sachet, Nayara M Bernhardt, Gislaine T Rezin, Samira S Valvassori, João Quevedo, Emilio L Streck
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  ABSTRACT: Methylphenidate is commonly used for the treatment of attention deficit/hyperactivity disorder. There are still few works regarding the effects of methylphenidate on brain energy metabolism. Thus, in the present study we evaluated the effect of chronic administration of methylphenidate on the activities of mitochondrial respiratory chain complexes I and III in the brain of young rats. The effect of acute administration of methylphenidate on mitochondrial respiratory chain complexes I, II, III and IV in the brain of young rats was also investigated. For acute administration, a single injection of methylphenidate was given to rats on postnatal day 25. For chronic administration, methylphenidate injections were given starting at postnatal day 25 once daily for 28 days. Our results showed that complexes I and III were not affected by chronic administration of methylphenidate. Moreover, the acute administration of methylphenidate decreased complex I activity in cerebellum and prefrontal cortex, whereas complexes II, III and IV were not altered.
  Neurochemical Research 11/2010; 35(11):1675-80. · 2.24 Impact Factor
• Article: Inhibitory avoidance task does not change NCS-1 level in rat brain.

  Daniela V F Rosa, Renan P Souza, Bruno R Souza, Fabrício F Lima, Samira S Valvassori, Marcus V Gomez, João Quevedo, Marco A Romano-Silva
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  ABSTRACT: Step-down inhibitory avoidance is usually acquired in one single trial, which makes it ideal for studying processes initiated by training, uncontaminated by prior or further trials, rehearsals, or retrievals. Neuronal calcium sensor 1 (NCS-1) is a dopamine receptor interacting protein that has been associated with associative learning and memory. We evaluated whether inhibitory avoidance can alter NCS-1 levels in rat brain. We focused our analysis on the striatum, entorhinal cortex, hippocampus and prefrontal cortex. Protein levels were measured using immunoblotting normalized by actin levels. Our results indicate that NCS-1 levels are not altered after step-down inhibitory avoidance in rat striatum, entorhinal cortex, hippocampus and prefrontal cortex. The link between protein interactions and the varied physiological roles of NCS-1 still remains to be fully established. Furthermore, other experiments are needed to shed more light on the role of NCS-1 and other mechanisms linked to signaling pathways related to inhibitory avoidance task.
  Brain research bulletin 07/2010; 82(5-6):289-92. · 2.18 Impact Factor
• Article: Role of oxidative stress in the pathophysiology of bipolar disorder.

  Amanda V Steckert, Samira S Valvassori, Morgana Moretti, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: In this work, we review the studies of oxidative stress markers, showing association with the pathophysiology of bipolar disorder (BD). BD is a prevalent, chronic and highly disabling psychiatric disorder. Several hypotheses have been postulated to explain the exact neurochemical mechanisms underlying the pathophysiology of BD, including a role for monoamines, gamma-amino butyric acid (GABA), glutamate, and second messenger singling pathways. More recently, oxidative stress has been implicated in the pathogenesis of BD. Recent studies have reported increased products of lipid peroxidation and alterations of the major antioxidants enzymes in patients with BD. It has been widely demonstrated that the generation of reactive oxygen species (ROS) plays a critical role in the pathophysiology of several neuropsychiatric disorders, such BD.
  Neurochemical Research 05/2010; 35(9):1295-301. · 2.24 Impact Factor
• Article: Evaluation of citrate synthase activity in brain of rats submitted to an animal model of mania induced by ouabain.

  Tiago P Freitas, Gislaine T Rezin, Cinara L Gonçalves, Gabriela C Jeremias, Lara M Gomes, Giselli Scaini, Brena P Teodorak, Samira S Valvassori, João Quevedo, Emilio L Streck
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  ABSTRACT: Bipolar disorder (BD) is a psychiatric disorder characterized by alternating episodes of mania and depression. The intracerebroventricular (i.c.v) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been used as an animal model of mania, because present face, construct and predictive validities. Several studies strongly suggest that mitochondrial dysfunction play a central role in the pathophysiology of BD. Citrate synthase (CS) is an enzyme localized in the mitochondrial matrix and represents one of the most important steps of Krebs cycle. The aim of this study was to investigate CS activity in brain of rats after the administration of ouabain. Adult male Wistar rats received a single i.c.v. administration of ouabain (10(-2) and 10(-3) M) or vehicle (control group). Locomotor activity was measured using the open field task. CS activity was measured in the brain of rats immediately (1 h) and 7 days after ouabain administration. Our results showed that spontaneous locomotion was increased 1 h after ouabain administration, and that the hyperlocomotion persists 7 days after the administration. Moreover, CS activity was inhibited immediately after the administration of ouabain in the prefrontal cortex at the doses of 10(-3) and 10(-2) M. This inhibition remains by 7 days after the administration of ouabain. On the other hand, it was not observed any difference in CS activity in the hippocampus and striatum. Considering that inhibition of CS activity may reflect a mitochondrial dysfunction, it is tempting to speculate that the reduction of brain energy metabolism might be related to the pathophysiology of BD.
  Molecular and Cellular Biochemistry 04/2010; 341(1-2):245-9. · 2.06 Impact Factor
• Article: Diurnal differences in memory and learning in young and adult rats treated with methylphenidate.

  Karin M Gomes, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Cecília G Inácio, Márcio R Martins, Renan P Souza, João Quevedo
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  ABSTRACT: Methylphenidate (MPH) is a very effective treatment option for children and adolescents with attention-deficit/hyperactivity disorder. Nevertheless, there have been inconsistent reports regarding the effects of MPH on learning and memory. The aim of this study was to evaluate whether the treatment with MPH during the morning differs from that during the night on learning and memory (short and long term) in young and adult male Wistar rats. The animals received once daily intraperitoneal injection of either MPH (2 mg/kg) or saline (0.9%) for 28 days (either in the morning or at night). The animals underwent two behavioral tasks to evaluate learning and memory: inhibitory avoidance task and continuous multiple trials step-down inhibitory avoidance (CMIA). Young rats treated in the morning showed significant impaired long-term memory for inhibitory avoidance training and facilitated acquisition in the CMIA. Adult rats treated in the night showed impaired long-term retention in the CMIA. We observed similar performances in both tests for young rats treated at night or adult rats treated in the morning. Our results suggest that age and time of treatment can alter the MPH effects in learning and memory.
  Acta Neurovegetativa 03/2010; 117(4):457-62. · 2.73 Impact Factor
• Article: Effects of moderate exercise on cigarette smoke exposure-induced hippocampal oxidative stress values and neurological behaviors in mice.

  Talita Tuon, Samira S Valvassori, Jéssica Lopes-Borges, Gabriel R Fries, Luciano A Silva, Flavio Kapczinski, João Quevedo, Ricardo A Pinho
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  ABSTRACT: The objective of the present study was to investigate the effects of exercise training on behavior and neurochemical parameters in mice exposed to cigarette smoke. To this aim, mice (C57 BL6) male (30-35 g) were exposed to cigarette smoke 60 consecutive days three times a day and they were subjected to treadmill training 8 weeks for 5 days/week. For behavior assessment, mice were tested in the open-field and forced to a swim test. The superoxide anion, thiobarbituric acid reactive substances and protein carbonyl formation were measured as markers of oxidative stress in hippocampus of mice. In addition, the brain-derived neurotrophic factor (BDNF) levels were measured in the hippocampus samples. Cigarette smoke group and cigarette smoke plus exercise group, increased immobility time in forced swimming test in rats compared to the control group, without affecting spontaneous locomotor activity. There was an increase in the levels of superoxide, TBARS and of protein carbonyl and a decreased in BDNF levels in the hippocampus of rats exposed to cigarette smoke and cigarette smoke plus exercise. Exercise alone did not change any of the parameters evaluated in this study. In conclusion, we observed that physical training improves the oxidative stress parameters, but does not alter depressive-like behavior neither prevent the decreases in BDNF levels in hippocampus induced by cigarette smoke.
  Neuroscience Letters 03/2010; 475(1):16-9. · 2.11 Impact Factor
• Article: Effects of mood stabilizers on mitochondrial respiratory chain activity in brain of rats treated with d-amphetamine.

  Samira S Valvassori, Gislaine T Rezin, Camila L Ferreira, Morgana Moretti, Cinara L Gonçalves, Mariana R Cardoso, Emílio L Streck, Flávio Kapczinski, João Quevedo
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  ABSTRACT: Bipolar disorder (BD) is a devastating major mental illness associated with high rates of suicide and work loss. There is an emerging body of data suggesting that bipolar disorder is associated with mitochondrial dysfunction. In this context, the present study aims to investigate the effects of mood stabilizers lithium (Li) and valproate (VPT) on mitochondrial respiratory chain activity in brain of rats undergoing treatment with the pro-manic agent d-AMPH d-amphetamine (d-AMPH). In the reversal treatment, Wistar rats were first given d-AMPH or saline for 14 days, and then, between days 8 and 14, rats were treated with Li, VPA or saline (Sal). In the prevention treatment, rats were pretreated with Li, VPA or Sal. Locomotor behavior was assessed using the open-field task and mitochondrial chain activity complexes I, II, III and IV were measured in brain structures (hippocampus, striatum and prefrontal). Li and VPA reversed and prevented d-AMPH-induced hyperactivity. In both experiments, d-AMPH inhibited mitochondrial respiratory chain activity in all analyzed structures. In the reversal treatment, VPA reversed d-AMPH-induced dysfunction in all brain regions analyzed. In the prevention experiment, the effects of Li and VPA on d-AMPH-induced mitochondrial dysfunction were dependent on the brain region analyzed. These findings suggested that dopamine can be an important link for the mitochondrial dysfunction seen in BD and, Li and VPA exert protective effects against this d-AMPH-induced mitochondrial dysfunction, but this effect varies depending on the brain region and the treatment regimen.
  Journal of psychiatric research 03/2010; 44(14):903-9. · 3.72 Impact Factor
• Article: Effects of a gastrin-releasing peptide receptor antagonist on D-amphetamine-induced oxidative stress in the rat brain.

  Samira S Valvassori, Morgana Moretti, Marcia Kauer-Sant'Anna, Rafael Roesler, Fabrícia Petronilho, Gilberto Schwartsmann, Flavio Kapczinski, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: Previous studies have suggested that bipolar disorder may be associated with oxidative stress. Administration of D: -amphetamine (AMPH) has been put forward as an animal model of mania, and has shown to increase oxidative stress parameters in the rat brain. Thus, we have used the gastrin-releasing peptide receptor antagonist [D-Tpi(6)Leu(13)psi (CH(2)NH)-Leu(14)] bombesin (RC-3095) as a pharmacological tool to investigate the role of bombesin-like peptides in the redox balance in the hippocampus and cortex of rats treated with AMPH. Rats were given a single 10 ml/kg intraperitoneal (i.p.) injection of saline (SAL) or RC-3095 (0.1, 1.0 or 10.0 mg/kg) followed by an i.p. injection of SAL or amphetamine (AMPH 2.0 mg/kg) 30 min later. Locomotor activity was evaluated 2 h after the last drug injection. The thiobarbituric acid reactive substances (TBARS), protein carbonyl formation, superoxide dismutase and catalase (CAT) activity were measured in hippocampus, striatum and cortex as markers of oxidative stress. The results show that RC-3095 blocks AMPH-induced hyperlocomotion. Moreover, specific doses of RC-3095 alone increased the levels of oxidative stress in the dorsal hippocampus and cortex. However, when AMPH was subsequently administrated, RC-3095 decreased TBARS and protein carbonyls formation and increased the superoxide dismutase and CAT activity in the hippocampus, striatum and cortex. The effects of GRPR antagonist seemed to be region and dose specific. In conclusion, the results suggest that GRPR antagonists might display antioxidant properties in the brain.
  Acta Neurovegetativa 03/2010; 117(3):309-16. · 2.73 Impact Factor
• Article: DNA damage after intracerebroventricular injection of ouabain in rats.

  Luciano K Jornada, Samira S Valvassori, Camila O Arent, Daniela Leffa, Adriani A Damiani, Giana Hainzenreder, Camila L Ferreira, Morgana Moretti, Vanessa M Andrade, João Quevedo
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  ABSTRACT: There is an emerging body of data suggesting that bipolar disorder is associated with DNA damage. Intracerebroventricular (i.c.v.) administration of ouabain in rats results in manic-like alterations. We evaluated DNA damage of peripheral blood, cerebrospinal fluid and hippocampus of rats after i.c.v. ouabain injection. Ouabain-induced hyperlocomotion was examined in an open field. Additionally, we used single cell gel electrophoresis (comet assay) to measure early transient damage in cerebrospinal fluid (CSF), hippocampus and blood; and the micronucleus test to measure persistent damage in total blood samples of rats after ouabain administration. Our findings demonstrated that ouabain induced hyperlocomotion in rats, and this response remained up to 7 days following a single i.c.v. injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased hippocampal and peripheral index of early DNA damage in rats. No significant alterations were observed in the micronucleus frequency in total blood samples of the rats after the ouabain i.c.v. injection. These results suggest that ouabain may induce peripheral and central early DNA damage, but this early damage may be repaired.
  Neuroscience Letters 02/2010; 471(1):6-9. · 2.11 Impact Factor
• Article: Intracerebroventricular ouabain administration induces oxidative stress in the rat brain.

  Rafael E Riegel, Samira S Valvassori, Morgana Moretti, Camila L Ferreira, Amanda V Steckert, Bruna de Souza, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: Intracerebroventricular (ICV) injection of ouabain (a potent Na(+)/K(+)-ATPase inhibitor) in rats resulted in manic-like effects. There is an emerging body of data indicating that major neuropsychiatric disorders, such as bipolar disorder and schizophrenia, are associated with increased oxidative stress. In this study, we investigated the effects of ICV ouabain injection on oxidative stress parameters in total tissue of rat brain. Our findings demonstrated that ICV injection increased thiobarbituric acid reactive species levels and protein carbonyl generation in the prefrontal cortex and hippocampus of rats. Moreover, the activity of the antioxidants enzymes catalase and superoxide dismutase was altered in several areas of the rat brain and cerebrospinal fluid of ICV ouabain-subjected rats. These results showed that Na(+)/K(+)-ATPase inhibition can lead to oxidative stress in the brain of rats.
  International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 02/2010; 28(3):233-7. · 2.03 Impact Factor
• Article: Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania.

  Samira S Valvassori, Guilherme Elias, Bruna de Souza, Fabrícia Petronilho, Felipe Dal-Pizzol, Flávio Kapczinski, Clarissa Trzesniak, Vitor Tumas, Serdar Dursun, Marcos Hortes Nisihara Chagas, Jaime E C Hallak, Antonio W Zuardi, João Quevedo, José A S Crippa
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  ABSTRACT: Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by D-amphetamine (D-AMPH). In the first model (reversal treatment), rats received saline or D-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or D-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.
  Journal of Psychopharmacology 11/2009; 25(2):274-80. · 3.04 Impact Factor
• Article: Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain.

  Luciano K Jornada, Morgana Moretti, Samira S Valvassori, Camila L Ferreira, Peterson T Padilha, Camila O Arent, Gabriel R Fries, Flavio Kapczinski, João Quevedo
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  ABSTRACT: There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
  Journal of psychiatric research 11/2009; 44(8):506-10. · 3.72 Impact Factor
• Article: Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats.

  Carina R Boeck, Virgínia B Marques, Samira S Valvassori, Leandra C Constantino, Daniela V F Rosa, Fabrício F Lima, Marco A Romano-Silva, João Quevedo
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  ABSTRACT: Chronic ingestion of caffeine causes dependence and sleep disturbance in children and adolescents. In rodents, the administration of caffeine may produce behavioral cross-sensitization to some psychostimulants, such as dopaminergic psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in pediatric- and adult human populations to manage the symptoms associated with attention-deficit hyperactivity disorder (ADHD). Previous studies have suggested that dopamine- and cAMP-regulated phosphoproteins of 32 kDa (DARPP-32) participate in the manifestation of behavioral activity following ingestion of caffeine or MPH. The aim of the present study was to evaluate whether long-term administration of low doses of caffeine in rodents during their adolescence induces cross-sensitization to MPH challenge in their adulthood and investigate the involvement of DARPP-32 in this model. Young rats (P25) consumed water or caffeine (0.3 g/L; mean consumption was 7.5 mg/day/kg) for 28 days. The caffeine consumption was then suspended for 14 days (washout period) when the animals received saline solution or MPH (1, 2, or 10 mg/kg) (P67) intraperitoneally. The locomotor activity of these rats was assessed using the open-field test, following which the immunocontent of DARPP-32 was evaluated in samples of their prefrontal cortex, striatum, or hippocampus. Rats chronically exposed to caffeine in their adolescent period and to inactive doses of MPH (1mg/kg) in adulthood showed augmented locomotor activity. The behavioral effect observed was accompanied by increased levels of DARPP-32 in the striatum and prefrontal cortex compared to control groups (saline or caffeine). However, no alteration caused by these treatments was noted in the hippocampus. In conclusion, chronic caffeine exposure induces likely long-term cross-sensitization to MPH in a DARPP-32-dependent pathway.
  Neurochemistry International 10/2009; 55(5):318-22. · 2.86 Impact Factor
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  Available from: Renan P Souza

  Article: Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests.

  Karin M Gomes, Renan P Souza, Samira S Valvassori, Gislaine Z Réus, Cecília G Inácio, Márcio R Martins, Clarissa M Comim, João Quevedo
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  ABSTRACT: In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.
  Current neurovascular research 10/2009; 6(4):259-66. · 3.23 Impact Factor
• Article: Superoxide production after acute and chronic treatment with methylphenidate in young and adult rats.

  Karin M Gomes, Cecília G Inácio, Samira S Valvassori, Gislaine Z Réus, Carina R Boeck, Felipe Dal-Pizzol, João Quevedo
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  ABSTRACT: The prescription of methylphenidate (MPH) has dramatically increased in this decade for attention deficit hyperactivity disorder (ADHD) treatment. The action mechanism of MPH is not completely understood and studies have been demonstrated that MPH can lead to neurochemical adaptations. Superoxide radical anion is not very reactive per se. However, severe species derived from superoxide radical anion mediate most of its toxicity. In this study, the superoxide level in submitochondrial particles was evaluated in response to treatment with MPH in the age-dependent manner in rats. MPH was administrated acutely or chronically at doses of 1, 2 or 10 mg/kg i.p. The results showed that the acute administration of MPH in all doses in young rats increased the production of superoxide in the cerebellum and only in the high dose (10mg/kg) in the hippocampus, while chronic treatment had no effect. However, acute treatment in adult rats had no effect on production of superoxide, but chronic treatment decreased the production of superoxide in the cerebellum at the lower doses. Our data suggest that the MPH treatment can influence on production of superoxide in some brain areas, but this effect depends on age of animals and treatment regime with MPH.
  Neuroscience Letters 09/2009; 465(1):95-8. · 2.11 Impact Factor
• Article: Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats.

  Lara C Assis, Gislaine T Rezin, Clarissa M Comim, Samira S Valvassori, Isabela C Jeremias, Alexandra I Zugno, João Quevedo, Emilio L Streck
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  ABSTRACT: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. The results showed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg) and imipramine (20 and 30mg/kg) increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity) by antidepressants could be an important mechanism of action of these drugs.
  Revista Brasileira de Psiquiatria 09/2009; 31(3):247-52. · 1.20 Impact Factor
• Article: Phosphoinositide 3-kinase is required for bombesin-induced enhancement of fear memory consolidation in the hippocampus.

  Rafael Roesler, Samira S Valvassori, Adalberto A Castro, Tatiana Luft, Gilberto Schwartsmann, João Quevedo
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  ABSTRACT: Increasing evidence indicates that the neuronal gastrin-releasing peptide-preferring bombesin receptor (GRPR) is a key molecular regulator of fear memory formation. However, the downstream signaling events remain poorly understood. The protooncogene product phosphoinositide 3-kinase (PI3K) has been implicated in regulating memory formation, as well as in mediating cellular responses to GRPR activation in glioma and neuroblastoma cells. We show here that GRPR modulation of fear memory consolidation in the rat hippocampus requires PI3K activation. Male Wistar rats received bilateral infusions of the GRPR agonist bombesin (BB) or the PI3K inhibitor LY294002 into the CA1 region of the dorsal hippocampus immediately after inhibitory avoidance (IA) conditioning. BB enhanced, whereas LY294002 impaired, IA memory retention. The BB-induced memory enhancement was blocked by coinfusion of either a GRPR antagonist or LY294002. These findings provide the first evidence suggesting that PI3K signaling is required for GRPR regulation of CNS function.
  Peptides 07/2009; 30(6):1192-6. · 2.43 Impact Factor
• Article: Ketamine treatment reverses behavioral and physiological alterations induced by chronic mild stress in rats.

  Lêda S B Garcia, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Laura Stertz, Flávio Kapczinski, Elaine C Gavioli, João Quevedo
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  ABSTRACT: Several studies have supported the idea that ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) is an important player in the etiology of psychopathologies, such as anxiety disorders and major depression. Additionally, studies have shown that ketamine induces antidepressant effects in humans as well as in rodents subjected to animal models of depression. In this context, the present study was aimed to evaluate behavioral and physiological effects of acute and chronic administration of ketamine, a NMDA receptor antagonist, in rats exposed to chronic mild stress (CMS). After 40 days of CMS, rats were treated with ketamine (15 mg/kg) and sweet food consumption, body and adrenal gland weight, corticosterone and adrenocorticotropic (ACTH) hormone levels, and hippocampal BDNF protein levels were assessed. Our findings demonstrated that CMS evoked anhedonia, induced hypertrophy of adrenal gland, impaired gain of body weight and increased corticosterone and ACTH circulating levels in rats. Acute and chronic treatment with ketamine reversed the increase in adrenal gland weight, promoted regain of body weight, and normalized corticosterone and ACTH circulating levels. Repeated, but not acute, administration of ketamine reversed anhedonia-like behavior, although the treatment with ketamine per se increased sweet food consumption in non-stressed rats. Finally, acute and chronic ketamine treatment did not alter hippocampal BDNF protein levels in stressed rats. In conclusion, these findings support the idea of a putative role of NMDA receptors in mood-related symptoms, and rapid and robust effects of ketamine in reverting mainly physiological alterations induced by chronic mild stressful situations in rats.
  Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2009; 33(3):450-5. · 3.25 Impact Factor
• Article: Effects of chronic mild stress on the oxidative parameters in the rat brain.

  Giancarlo Lucca, Clarissa M Comim, Samira S Valvassori, Gislaine Z Réus, Francieli Vuolo, Fabrícia Petronilho, Felipe Dal-Pizzol, Elaine C Gavioli, João Quevedo
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  ABSTRACT: Major depression is characterized for symptoms at the psychological, behavioral and physiological levels. The chronic mild stress model has been used as an animal model of depression. The consumption of sweet food, locomotor activity, body weight, lipid and protein oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, prefrontal cortex and cortex were assessed in rats exposed to chronic mild stress. Our findings demonstrated a decrease on sweet food intake, no effect on locomotor activity, lack of body weight gain, increase in protein (prefrontal, hippocampus, striatum and cortex) and lipidic peroxidation (cerebellum and striatum), and an increase in catalase (cerebellum, hippocampus, striatum, cortex) and a decrease in superoxide dismutase activity (prefrontal, hippocampus, striatum and cortex) in stressed rats. In conclusion, our results support the idea that stress produces oxidants and an imbalance between superoxide dismutase and catalase activities that contributes to stress-related diseases, such as depression.
  Neurochemistry International 02/2009; 54(5-6):358-62. · 2.86 Impact Factor