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059 — (PRO0041) Adolescent mice are more vulnerable than adults to the rewarding effects of ecstasy (MDMA)
Abstracts
Discussion/conclusions: Our findings suggest that the group with IPIF+ was different from the group with IPIF− regarding neuropathological features and clinical and 3-T MRI data. These parameters might play a role in the physiopathology of RMTLE–HS with history of FS. Acknowledgments/financial support: This work was supported by FAPESP, Brazil. doi:10.1016/j.yebeh.2014.08.090
058 — (PRE0114) Nitroalkenes induce neuroprotection against pilocarpine-induced temporal lobe epilepsy G.M. Predebona, M.G.L. Araujoa, L.F.S. Araújoa, M.J.S. Fernandesa, J.L. Netob, J.V. Comassetoc a Universidade Federal de São Paulo, Departamento de Neurologia/ Neurocirurgia, Brazil b Universidade Federal de São Paulo, Departamento de Biofísica, Brazil c Universidade Federal de São Paulo, Instituto de Química, Departamento de Química Fundamental, Brazil Rationale: Temporal lobe epilepsy (TLE) is a form of intractable epilepsy in humans. The pathophysiology of TLE includes hippocampal sclerosis with cell death in CA1, CA3 and the hilus with reactional gliosis. Caspase activation is a mechanism involved in cell death induced by seizures. Temporal lobe epilepsy can be induced in rats by pilocarpine. Nitroalkenes are nitrated unsaturated fatty acids that can be detected in healthy human plasma, red blood cells, and urine. Some authors have shown that nitroalkenes have potent antiinflammatory, antiapoptotic, and immunomodulatory properties in multiple disease models. This study was performed to investigate the effects of nitroalkenes 1, 3, 8, and 13 on cell damage caused by pilocarpine in rats. Methods: Wistar male rats, adults, were used in this study. The nitroalkenes (500 μg/kg) were administrated (i.p.) sequentially 30 min, 6 h, 12 h, and 18 h after status epilepticus (SE) induced by pilocarpine (360 mg/kg, i.p.) and studied 24 h after the last injection to evaluate cell death by Fluoro-Jade B. Results: Nitroalkenes 8 and 13 reduced the severity of epileptic seizures, while 1 and 3 increased their severity. Treatments with the nitroalkenes 8 and 13 were able to reduce neuronal death in hippocampal subareas CA1, CA3, GD, and hilus compared with nontreated rats. Discussion/conclusions: These results are preliminary and indicate that nitroalkenes may represent a new potential therapy for TLE. Keywords: Temporal lobe epilepsy, pilocarpine, nitroalkenes. Acknowledgments/financial supports: We thank CAPES, FAPESP, CNPq, INNT/Fapesp, and Pronex/Fapesp for financial support and Hilda Silva Reis for technical support. doi:10.1016/j.yebeh.2014.08.091
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aim of the present study was to investigate, in adolescent and adult mice, the effects of MDMA on the CPP procedure. Methods: The study was conducted using adolescent (30 days old) and adult (90 days old) male C57BL/6 mice. Mice were submitted to the CPP procedure in all the experiments. The dose of MDMA and the amount of conditioning sessions varied across the experiments. Briefly, the animals received an i.p. injection of MDMA and, 20 min later, were confined for 15 min in one compartment of the apparatus (half of the animals of each group were confined in compartment A and the other half in compartment B — unbiased design). Six hours later, these animals received an i.p. injection of saline and were confined for 15 min in the other compartment (different to the one where they had received MDMA). Twenty-four hours after the conditioning procedure, animals were given free access to all the compartments of the apparatus and the time spent in each compartment was quantified for 15 min. In experiment 1, adolescent and adult mice were submitted to the CPP procedure with an ineffective dose of MDMA (5 mg/kg). A total of 2 sessions with the drug and 2 sessions with saline were performed. In experiment 2, the same protocol of experiment 1 was used except that the dose of MDMA was increased to 10 mg/kg. In experiment 3, the same protocol of experiment 1 was used except that the conditioning sessions were increased to a total of 4 sessions with the drug and 4 sessions with saline. Results: Within-group comparisons were performed using the T-test for paired samples. In experiment 1, neither adolescents nor adults developed CPP to 5 mg/kg MDMA after 2-drug-conditioning sessions. In experiment 2, increasing the dose of MDMA (10 mg/kg) led to the development of MDMA-induced CPP only in adolescent mice (as evidenced by an increase in the time spent in the drug-paired compartment relative to the salinepaired compartment [t(9) = 2.4, 3.2, and 2.1, p b 0.05, for 0–5, 0–10, and 0–15 min, respectively]). In experiment 3, when the number of conditioning sessions was increased to 4, only adolescent mice presented MDMA-induced CPP (as evidenced by an increase in the time spent in the drug-paired compartment relative to the saline-paired compartment [t(9) = 2.3 and 2.9, p b 0.05, for 0–10 and 0–15 min, respectively]). Discussion/conclusions: Our data indicated that an ineffective dose of MDMA (5 mg/kg) may induce CPP in adolescent mice if the number of conditioning sessions is increased. In addition, enhancing the dose of MDMA (10 mg/kg) is sufficient to produce CPP in adolescent mice even if the number of conditioning sessions is maintained constant. These findings suggest that adolescents are more sensitive than adults to the rewarding effects of MDMA. Acknowledgments/financial support: CAPES, CNPq, FAPESP, and AFIP. doi:10.1016/j.yebeh.2014.08.092
060 — (RAM0050) Hyperactivity behavior and visual task in animals with temporal lobe epilepsy F.O. Ramosa, F.A. Scorzaa, R.M. Cysneirosa,b UNIFESP, Brazil b Laboratory of Neurobiology, Presbyterian University Mackenzie, Brazil
a
059 — (PRO0041) Adolescent mice are more vulnerable than adults to the rewarding effects of ecstasy (MDMA) R. Procopio-Souza, T.F. Trombin, E. Mári-Kawamoto, R. Wuo-Silva, J.M. Costa, S.R. Kameda, D.F. Fukushiro, R. Frussa-Filho UNIFESP, Brazil Rationale: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is an illicit recreational psychostimulant consumed by many teenagers and adults. In parallel, it has been demonstrated that drugs with abuse potential induce conditioned place preference (CPP), an animal model to evaluate the rewarding properties of drugs, in rodents. Therefore, the
Rationale: Temporal lobe epilepsy (TLE) can have a substantial impact on cognitive processes. The prevalence of attention deficit hyperactivity disorder (ADHD) in children with epilepsy is estimated to be from 12 to 39%, but the relationship between these two diseases is poorly understood and no validated animal models are available to explore this issue. This study investigated the cognitive flexibility, performance on visual task, and hyperactivity of animals with TLE. Methods: Male Wistar rats at 25 postnatal days were submitted to the epilepsy model by systemic administration of pilocarpine, while controls received 0.9% saline. Diazepam (7.5 mg/kg, sc) was administered 3 h after the onset of status epilepticus to stop or reduce behavioral seizures.
Discussion/conclusions: Our findings suggest that the group with IPIF+ was different from the group with IPIF− regarding neuropathological features and clinical and 3-T MRI data. These parameters might play a role in the physiopathology of RMTLE–HS with history of FS. Acknowledgments/financial support: This work was supported by FAPESP, Brazil. doi:10.1016/j.yebeh.2014.08.090
058 — (PRE0114) Nitroalkenes induce neuroprotection against pilocarpine-induced temporal lobe epilepsy G.M. Predebona, M.G.L. Araujoa, L.F.S. Araújoa, M.J.S. Fernandesa, J.L. Netob, J.V. Comassetoc a Universidade Federal de São Paulo, Departamento de Neurologia/ Neurocirurgia, Brazil b Universidade Federal de São Paulo, Departamento de Biofísica, Brazil c Universidade Federal de São Paulo, Instituto de Química, Departamento de Química Fundamental, Brazil Rationale: Temporal lobe epilepsy (TLE) is a form of intractable epilepsy in humans. The pathophysiology of TLE includes hippocampal sclerosis with cell death in CA1, CA3 and the hilus with reactional gliosis. Caspase activation is a mechanism involved in cell death induced by seizures. Temporal lobe epilepsy can be induced in rats by pilocarpine. Nitroalkenes are nitrated unsaturated fatty acids that can be detected in healthy human plasma, red blood cells, and urine. Some authors have shown that nitroalkenes have potent antiinflammatory, antiapoptotic, and immunomodulatory properties in multiple disease models. This study was performed to investigate the effects of nitroalkenes 1, 3, 8, and 13 on cell damage caused by pilocarpine in rats. Methods: Wistar male rats, adults, were used in this study. The nitroalkenes (500 μg/kg) were administrated (i.p.) sequentially 30 min, 6 h, 12 h, and 18 h after status epilepticus (SE) induced by pilocarpine (360 mg/kg, i.p.) and studied 24 h after the last injection to evaluate cell death by Fluoro-Jade B. Results: Nitroalkenes 8 and 13 reduced the severity of epileptic seizures, while 1 and 3 increased their severity. Treatments with the nitroalkenes 8 and 13 were able to reduce neuronal death in hippocampal subareas CA1, CA3, GD, and hilus compared with nontreated rats. Discussion/conclusions: These results are preliminary and indicate that nitroalkenes may represent a new potential therapy for TLE. Keywords: Temporal lobe epilepsy, pilocarpine, nitroalkenes. Acknowledgments/financial supports: We thank CAPES, FAPESP, CNPq, INNT/Fapesp, and Pronex/Fapesp for financial support and Hilda Silva Reis for technical support. doi:10.1016/j.yebeh.2014.08.091
207
aim of the present study was to investigate, in adolescent and adult mice, the effects of MDMA on the CPP procedure. Methods: The study was conducted using adolescent (30 days old) and adult (90 days old) male C57BL/6 mice. Mice were submitted to the CPP procedure in all the experiments. The dose of MDMA and the amount of conditioning sessions varied across the experiments. Briefly, the animals received an i.p. injection of MDMA and, 20 min later, were confined for 15 min in one compartment of the apparatus (half of the animals of each group were confined in compartment A and the other half in compartment B — unbiased design). Six hours later, these animals received an i.p. injection of saline and were confined for 15 min in the other compartment (different to the one where they had received MDMA). Twenty-four hours after the conditioning procedure, animals were given free access to all the compartments of the apparatus and the time spent in each compartment was quantified for 15 min. In experiment 1, adolescent and adult mice were submitted to the CPP procedure with an ineffective dose of MDMA (5 mg/kg). A total of 2 sessions with the drug and 2 sessions with saline were performed. In experiment 2, the same protocol of experiment 1 was used except that the dose of MDMA was increased to 10 mg/kg. In experiment 3, the same protocol of experiment 1 was used except that the conditioning sessions were increased to a total of 4 sessions with the drug and 4 sessions with saline. Results: Within-group comparisons were performed using the T-test for paired samples. In experiment 1, neither adolescents nor adults developed CPP to 5 mg/kg MDMA after 2-drug-conditioning sessions. In experiment 2, increasing the dose of MDMA (10 mg/kg) led to the development of MDMA-induced CPP only in adolescent mice (as evidenced by an increase in the time spent in the drug-paired compartment relative to the salinepaired compartment [t(9) = 2.4, 3.2, and 2.1, p b 0.05, for 0–5, 0–10, and 0–15 min, respectively]). In experiment 3, when the number of conditioning sessions was increased to 4, only adolescent mice presented MDMA-induced CPP (as evidenced by an increase in the time spent in the drug-paired compartment relative to the saline-paired compartment [t(9) = 2.3 and 2.9, p b 0.05, for 0–10 and 0–15 min, respectively]). Discussion/conclusions: Our data indicated that an ineffective dose of MDMA (5 mg/kg) may induce CPP in adolescent mice if the number of conditioning sessions is increased. In addition, enhancing the dose of MDMA (10 mg/kg) is sufficient to produce CPP in adolescent mice even if the number of conditioning sessions is maintained constant. These findings suggest that adolescents are more sensitive than adults to the rewarding effects of MDMA. Acknowledgments/financial support: CAPES, CNPq, FAPESP, and AFIP. doi:10.1016/j.yebeh.2014.08.092
060 — (RAM0050) Hyperactivity behavior and visual task in animals with temporal lobe epilepsy F.O. Ramosa, F.A. Scorzaa, R.M. Cysneirosa,b UNIFESP, Brazil b Laboratory of Neurobiology, Presbyterian University Mackenzie, Brazil
a
059 — (PRO0041) Adolescent mice are more vulnerable than adults to the rewarding effects of ecstasy (MDMA) R. Procopio-Souza, T.F. Trombin, E. Mári-Kawamoto, R. Wuo-Silva, J.M. Costa, S.R. Kameda, D.F. Fukushiro, R. Frussa-Filho UNIFESP, Brazil Rationale: 3,4-Methylenedioxymethamphetamine (MDMA), or ecstasy, is an illicit recreational psychostimulant consumed by many teenagers and adults. In parallel, it has been demonstrated that drugs with abuse potential induce conditioned place preference (CPP), an animal model to evaluate the rewarding properties of drugs, in rodents. Therefore, the
Rationale: Temporal lobe epilepsy (TLE) can have a substantial impact on cognitive processes. The prevalence of attention deficit hyperactivity disorder (ADHD) in children with epilepsy is estimated to be from 12 to 39%, but the relationship between these two diseases is poorly understood and no validated animal models are available to explore this issue. This study investigated the cognitive flexibility, performance on visual task, and hyperactivity of animals with TLE. Methods: Male Wistar rats at 25 postnatal days were submitted to the epilepsy model by systemic administration of pilocarpine, while controls received 0.9% saline. Diazepam (7.5 mg/kg, sc) was administered 3 h after the onset of status epilepticus to stop or reduce behavioral seizures.