Electroacupuncture reverses ethanol-induced locomotor sensitization and subsequent pERK expression in mice

Extracellular signal-regulated kinase (ERK) plays a role in neuronal changes induced by repeated drug exposure. Given that electroacupuncture reverses locomotor sensitization induced by ethanol, we investigated whether this effect is parallel to ERK signalling. Mice received daily ethanol (2 g/kg i.p), for 21 d. Electroacupuncture was performed daily, during four (subsequent) days of ethanol withdrawal. the stimulus of 2 Hz or 100 Hz was provided in combinations of two acupoints: Ea1 (ST-36/Zusanli and PC-6/Neiguan) or Ea2 (Du-14/Dazhui and Du-20/Baihui). the specificity of acupoint effects were assessed by the inclusion of additional groups: Ea3 (ST-25/Tianshu - acupoint used for other non-related disorders), Sham1 or Sham2 (transdermic stimulation near the respective acupoints). the control group was only handled during withdrawal and the saline group was chronically treated with saline and handled similarly to controls. At day 5 of withdrawal, each group was divided in two subgroups, according to the presence or absence of ethanol challenge. the animals were perfused and their brains processed for pERK immunohistochemistry. Only Ea1 at 100 Hz (Ea1_100) and Ea2 at 2 Hz (Ea2_2) reversed locomotor sensitization induced by ethanol. Ethanol withdrawal decreases pERK in the dorsomedial striatum. This decrease is not abolished by electroacupuncture. Conversely, ethanol challenge increases pERK in the dorsomedial striatum, infralimbic cortex and central nucleus of amygdala. the specificity of acupoint stimulation to reverse these increases was seen only for Ea2_2, in the infralimbic cortex and dorsomedial striatum. Therefore, behavioural effects of Ea2_2 (but not Ea1_100) depend, at least in part, on ERK signalling.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Neurobiol Lab, Grp Neuronal Plast & Psychiat Disorders, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Orthoped & Traumatol, Div Chinese Med Acupuncture, São Paulo, BrazilFac Med Sci, Dept Physiol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, Grp Neuronal Plast & Psychiat Disorders, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Orthoped & Traumatol, Div Chinese Med Acupuncture, São Paulo, BrazilFAPESP: 2010-03896-7FAPESP: 2007/55458-0Web of Scienc

Em uma encruzilhada: potencial do nível plasmático de lítio como preditor da dose ideal

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255%, or 0.383% of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255% lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50% higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.OBJETIVO: Além de ser usado há décadas para tratar distúrbio bipolar, o lítio, mais recentemente, demonstrou-se eficaz para Alzheimer, síndrome de Down, processos isquêmicos e excitotoxicidade mediada por glutamato. Contudo, a estreita janela terapêutica do lítio limita seu uso. Portanto, o estabelecimento de métodos preditivos de dose torna-se importante. MÉTODO: O desempenho de ratos Wistar adultos foi avaliado no campo aberto e labirinto em cruz elevado após seis semanas de tratamento com uma ração suplementada com 0,255% ou 0,383% de cloreto de lítio ou ração normal. Coletou-se amostras de sangue para dosagem plasmática do lítio. RESULTADOS: Os animais alimentados com a ração com 0,255% de cloreto de lítio fizeram mais rearing no campo aberto e tiveram uma maior freqüência de entradas nos braços do labirinto elevado que os animais que ingeriram a dose mais alta. Apesar disso, verificou-se níveis plasmáticos de lítio semelhantes em ambos os grupos. DISCUSSÃO: A variação nos comportamentos destarte a presença de níveis plasmáticos semelhantes sugere que as diferentes doses produziram diferentes concentrações cerebrais não detectadas pela medida plasmática. CONCLUSÃO: Medidas da concentração plasmática de lítio não permitem prever de forma completa seus efeitos comportamentais.Universidade Federal de São Paulo (UNIFESP) Department of PhysiologyUNIFESP, Department of PhysiologySciEL

Intermittent ethanol binge exposure impairs object recognition but spares contextual and tone fear memory in adolescent rats

Adolescent brain development seems to be important for the maturation of brain structures and behavior. Intermittent binge ethanol drinking is common among adolescents, and this type of drinking can induce brain damage and cognitive deficits. In addition, emotional changes are frequently seen in alcoholics and rodents treated with ethanol. Considering the close relation between emotional arousal and cognitive responses, the present work investigates if intermittent ethanol binge exposure could differentially alter the performance of adolescent rats in aversive and non-aversive motivated tests. Male adolescent rats were submitted to ethanol treatment (2.5 or 5.0 g/Kg, o.a.) at 48-h intervals over postnatal day (PND) 30 to 60. Control animals were exposed to a similar administration protocol with saline administration. At PND61-PND63 animals were submitted to one-trial object recognition or contextual and tone fear conditioning paradigms. Binge ethanol drinking (at both 2.5 and 5.0 g/Kg) did not change freezing response in the contextual and tone fear conditioning. However, all doses impaired recognition rates 24h after training in object recognition test. In addition, despite a diminution of horizontal locomotion in the open field (only for the 5.0 g/Kg dose), no difference was detected regarding time in immobility, time in grooming and number of rearing in this paradigm. The present results show that the cognitive impairment resulting from intermittent binge ethanol exposure has a negative correlation with learning-associated emotional arousal.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Santa Casa de São Paulo Faculdade de Ciências MédicasUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Withdrawal induces distinct patterns of FosB/Delta FosB expression in outbred Swiss mice classified as susceptible and resistant to ethanol-induced locomotor sensitization

Chronic drug exposure and drug withdrawal induce expressive neuronal plasticity which could be considered as both functional and pathological responses. It is well established that neuronal plasticity in the limbic system plays a pivotal role in relapse as well as in compulsive characteristics of drug addiction. Although increases in FosB/DeltaFosB expression constitute one of the most important forms of neuronal plasticity in drug addiction, it is unclear whether they represent functional or pathological plasticity. It is of noteworthy importance the individual differences in the transition from recreational use to drug addiction. These differences have been reported in studies involving the ethanol-induced locomotor sensitization paradigm. in the present study we investigated whether sensitized and non-sensitized mice differ in terms of FosB/DeltaFosB expression. Adult male outbred Swiss mice were daily treated with ethanol or saline for 21 days. According to the locomotor activity in the acquisition phase, they were classified as sensitized (EtOH_High) or non-sensitized (EtOH_Low). After 18 h or 5 days, their brains were processed for FosB/DeltaFosB immunohistochemistry. On the 5th day of withdrawal, we could observe increased FosB/DeltaFosB expression in the EtOH_High group (in the motor cortex), in the EtOH_Low group (in the ventral tegmental area), and in both groups (in the striatum). Differences were more consistent in the EtOH_Low group. Therefore, behavioral variability observed in the acquisition phase of ethanol-induced locomotor sensitization was accompanied by differential neuronal plasticity during withdrawal period. Furthermore, distinct patterns of FosB/DeltaFosB expression detected in sensitized and non-sensitized mice seem to be more related to withdrawal period rather than to chronic drug exposure. Finally, increases in FosB/DeltaFosB expression during withdrawal period could be considered as being due to both functional and pathological plasticity. (C) 2013 Elsevier Inc. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Psychiat & Med Psychol, BR-04038020 São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, BR-04039032 São Paulo, BrazilFac Med Sci Santa Casa São Paulo, Dept Physiol Sci, BR-01221020 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat & Med Psychol, BR-04038020 São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, BR-04039032 São Paulo, BrazilWeb of Scienc

Analysis of Production and Consumption of Electric Energy in the Green Office of UTFPR in Curitiba

ABSTRACT The increasing demand for electricity and the scarcity of resources, require renewable energy sources and efficient equipment that reduce the consumption of electricity. The Green Office (GO) of the Universidade Tecnológica Federal do Paraná (UTFPR) is a sustainable building that uses strategies to reduce impacts to the environment, one of them being the use of the grid connected photovoltaic system (on-grid). The on-grid was installed in 2011 and since then has been feeding the GO and another building (block V) belonging to UTFPR. This article presents a comparison between an estimate of energy consumption and the generation of energy through the on-grid. By means of the estimated consumption, a survey in loco of the scenario of expenditures of the electrical equipment used in the GO was made, estimating hours of use and power, so the consumption scenario was 145 kWh/month. The power generation of the EV is lower in the months May - July, period in which the solar irradiation is smaller, but according to the measurements the on-grid produces more energy than it consumes

Systematic review of the literature on clinical and experimental trials on the antitumor effects of cannabinoids in gliomas

To evaluate, through a systematic review of the literature, the antitumoral effects of cannabinoids on gliomas. Research included the following electronic databases: PUBMED, EMBASE, LILACS and the Cochrane Collaboration Controlled Trials Register. All published studies involving the antitumoral effects (cellular and molecular mechanisms) of cannabinoids were considered for this review. the bibliography search strategy included all publications of each of these databases until December 31, 2012. From 2,260 initially identified articles, 35 fulfilled the inclusion criteria for this review. All the studies included in this systematic review were experimental (in vivo and/or in vitro), except for one pilot clinical trial phase I/II involving humans. in all experimental studies included, cannabinoids exerted antitumoral activity in vitro and/or antitumoral evidence in vivo in several models of tumor cells and tumors. the antitumor activity included: antiproliferative effects (cell cycle arrest), decreased viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well as antiangiogenic and antimigratory effects. Antitumoral evidence included: reduction in tumor size, antiangiogenic, and antimetastatic effects. Additionally, most of the studies described that the canabinnoids exercised selective antitumoral action in several distinct tumor models. Thereby, normal cells used as controls were not affected. the safety factor in the cannabinoids' administration has also been demonstrated in vivo. the various cannabinoids tested in multiple tumor models showed antitumoral effects both in vitro and in vivo. These findings indicate that cannabinoids are promising compounds for the treatment of gliomas.Universidade Federal de São Paulo, Paulista Sch Med, BR-04027000 São Paulo, BrazilFac Med Sci Santa Casa São Paulo, BR-04025001 São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, BR-04027000 São Paulo, BrazilWeb of Scienc

Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. the aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57b1/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. the low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization. (C) 2015 Elsevier B.V. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)INCT-National Institute of Science and Technology for Excitotoxicity and NeuroprotectionUniv Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Neurol & Neurosci Grad Program, São Paulo, BrazilSanta Casa Sch Med Sci, Dept Physiol Sci, São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Neurol & Neurosci Grad Program, São Paulo, BrazilFAPESP: FAPESP-2009/16305-0Web of Scienc