Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis / 法医学杂志

OBJECTIVES@#To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis.@*METHODS@#SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins.@*RESULTS@#The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells.@*CONCLUSIONS@#CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.

Circulación de información sobre medicamentos y otras sustancias para aumentar el rendimiento cognitivo: un estudio de un blog brasileño (2015-2017) / Circulation of information on drugs and other substances to increase cognitive performance: a study of a Brazilian blog (2015-2017)

RESUMEN Al observar los procesos de (bio)medicalización y farmacologización de la sociedad, este artículo aborda los medicamentos que han sido utilizados por individuos sanos para aumentar sus dimensiones cognitivas, como el estado de alerta, la memoria y la concentración. Las llamadas "drogas inteligentes" o "drogas nootrópicas" se han extendido entre los jóvenes a través de Internet. La circulación de información sobre tales drogas se analiza desde un blog brasileño llamado Cérebro Turbinado, sobre el que se realizó una investigación documental basada en el material publicado en el blog entre 2015 y 2017, de acceso público. La investigación adopta marcos teóricos y metodológicos de las ciencias sociales, junto a una perspectiva antropológica. Los resultados muestran que el blog actúa como un medio para la difusión del conocimiento biomédico entre el público lego y muestra la producción de nuevas formas de subjetividad al revelar los significados que se atribuyen a tales sustancias en los procesos de socialización.

ABSTRACT By observing the processes of (bio)medicalization and pharmaceuticalization of society, this article addresses drugs that have been used by healthy individuals to increase cognitive dimensions such as alertness, memory, and concentration. The use of so-called "smart drugs" or "nootropics" has spread among young people, aided by the internet. The circulation of information about such drugs are analyzed using a Brazilian blog called "Cérebro Turbinado," through publications available for public access between 2015 and 2017. The study adopts theoretical and methodological frameworks of the social sciences, including an anthropological perspective. Documental research was conducted on the internet, specifically with scientific dissemination materials and the material available from the aforementioned blog. The results show that the blog acts as a medium for spreading biomedical knowledge among the lay public and indicates the production of new forms of subjectivity by revealing the meanings attributed to these substances in socialization processes.

Effects of N-acetylcysteine on amphetamine-induced sensitization in mice

Objective: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. Methods: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. Results: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Conclusion: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification.

Effect of caffeine on vestibular evoked myogenic potential: a systematic review with meta-analysis / Efeito da cafeína no potencial evocado miogênico vestibular: uma revisão sistemática com metanálise

Abstract Introduction: Caffeine can be considered the most consumed drug by adults worldwide, and can be found in several foods, such as chocolate, coffee, tea, soda and others. Overall, caffeine in moderate doses, results in increased physical and intellectual productivity, increases the capacity of concentration and reduces the time of reaction to sensory stimuli. On the other hand, high doses can cause noticeable signs of mental confusion and error induction in intellectual tasks, anxiety, restlessness, muscle tremors, tachycardia, labyrinthine changes, and tinnitus. Objective: Considering that the vestibular evoked myogenic potential is a clinical test that evaluates the muscular response of high intensity auditory stimulation, the present systematic review aimed to analyze the effects of caffeine on vestibular evoked myogenic potential. Methods: This study consisted of the search of the following databases: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov. Additionally, the gray literature was also searched. The search strategy included terms related to intervention (caffeine or coffee consumption) and the primary outcome (vestibular evoked myogenic potential). Results: Based on the 253 potentially relevant articles identified through the database search, only two full-text publications were retrieved for further evaluation, which were maintained for qualitative analysis. Conclusion: Analyzing the articles found, caffeine has no effect on vestibular evoked myogenic potential in normal individuals.

Resumo Introdução: A cafeína pode ser considerada a droga mais consumida por adultos em nível mundial, podendo ser encontrada em inúmeros alimentos, como no chocolate, café, chá, refrigerante e outros. Em geral, a cafeína em doses moderadas, produz ótimos rendimentos físico e intelectual, aumenta a capacidade de concentração e diminui o tempo de reação aos estímulos sensoriais. Por outro lado, doses elevadas podem causar sinais perceptíveis de confusão mental e indução de erros em tarefas intelectuais, ansiedade, nervosismo, tremores musculares, taquicardia, alterações labirínticas e zumbido. Objetivo: Considerando que o potencial evocado miogênico vestibular é um teste clínico que avalia a resposta muscular decorrente de estimulação auditiva de alta intensidade, a presente revisão sistemática objetivou analisar o efeito da cafeína sobre o potencial evocado miogênico vestibular. Método: A formulação deste trabalho consistiu na busca dos estudos nas seguintes bases de dados: MEDLINE, CENTRAL, ScienceDirect, Scopus, Web of Science, LILACS, SciELO e Clinical-Trials.gov. Adicionalmente, a literatura cinzenta também foi pesquisada. A estratégia de busca incluiu termos relacionados à intervenção (consumo de cafeína ou café) e ao desfecho primário (potencial evocado miogênico vestibular). Resultados: A partir de 253 registros potencialmente relevantes identificados através da busca nas bases de dados, apenas duas publicações em texto completo foram recuperadas para avaliação mais aprofundada, sendo estas mantidas para a análise qualitativa. Conclusão: Diante dos artigos encontrados a cafeína não tem efeito sobre o potencial evocado miogênico vestibular em sujeitos normais.

Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility / Transtorno do déficit de atenção/hiperatividade (TDAH): o impacto do metilfenidato na memória operacional, capacidade inibitória e flexibilidade mental

ABSTRACT Objective To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Methods Neuropsychological tests were administrated to 53 boys, 9–12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and with normal intelligence without comorbidities. The control group (n = 30) were age and gender matched. After three months on methylphenidate, the ADHD children were retested. The control group was also retested after three months. Results Before treatment, ADHD children had lower scores than the control group on the tests (p ≤ 0.001) and after methylphenidate had fewer test errors than before (p ≤ 0.001) Conclusion Methylphenidate treatment improves the working memory, inhibitory control and mental flexibility of ADHD boys.

RESUMO Objetivo Comparar crianças com transtorno de déficit de atenção/hiperatividade (TDAH) com controles, utilizando testes de memória de trabalho, capacidade inibitória e flexibilidade mental, em meninos de 9 a 12 anos. Métodos Testes neuropsicológicos administrados: teste de ordem inversa dos dígitos, teste aritmético (WISC-III), Teste Stroop e Teste de Trilhas. Grupo experimental meninos (n=23), com TDAH combinado, virgens de tratamento, inteligência normal sem comorbidades. Grupo controle (n = 30) com as mesmas características do grupo experimental em termos de idade e sexo. Após três meses com metilfenidato, os grupos TDAH e controle foram novamente testadas. Resultados Antes do tratamento, as crianças com TDAH apresentaram menor pontuação do que o grupo controle nos testes analisados (p≤ 0.001) e o grupo com TDAH apresentou menos erros nos testes após metilfenidato (p ≤ 0.001). Conclusão O tratamento com metilfenidato melhora a memória de trabalho, controle inibitório e flexibilidade mental de meninos com TDAH.

The effect of caffeine supplementation on exercise performance evaluated by a novel animal model

Introduction: Caffeinated drinks are used for improve performance. Animal models represent investigational strategy that circumvents most of the drawbacks of research in humans, including motivational factors and the placebo effect. No animal model that could test whether different forms of administering caffeine affect exercise propensity was found in the literature. Methods: An animal model of grouped voluntary exercise was tested. Two-month-old male C57/bl mice were housed in a cage fitted with one running wheel and a monitoring system. Six animals per cage were introduced individually. To assess the sensitivity of the model, the effect of different caffeinated drinks was observed in mice exercising ad libitum. During 2 days, the mice received: 1) pure anhydrous caffeine 0.125 mg/mL (PC), 2) cola drink (CC), and 3) caffeine-taurine-glucuronolactone drink (CTG), intercalating wash-out periods of 2 days, receiving pure water. Results: The distance run during the periods of water ingestion was significantly lower than during the periods of stimulant drinks ingestion: PC (5.6 ± 1.3 km; p = 0.02), of CC ingestion (7.6 ± 0.6 km; p = 0.001), and of CTG ingestion (8.3 ± 1.6 km; p = 0.009). The performances when ingesting the three caffeinated drinks do not follow a dose-response curve. Conclusions: The model described here was able to measure the effect of caffeine intake on voluntary exercise of mice. The sensitivity of the model to the effect of caffeine needs to be further validated. The action of each component of the drinks on exercise performance needs to be clarified in future research. The present model is adequate for such investigation (AU)

As controvérsias sócio-históricas das práticas farmacológicas com o metilfenidato / Las controversias socio-históricas de las prácticas farmacológicas con metilfenidato / The socio-historical controversies in pharmacological practices with methylphenidate

Resumo O metilfenidato, principal substância utilizada no tratamento farmacológico do Transtorno do Défict de Atenção e Hiperatividade (TDAH), é atualmente o psicoestimulante mais consumido no mundo e assunto constante na mídia e nas produções científicas em Psicologia e Psiquiatria. Neste artigo, discutimos alguns elementos do discurso científico sobre esse medicamento, nos servindo de elementos históricos, ricos em controvérsias, para propor sua emergência como problema, conforme indica Foucault. Assim, analisamos a diversidade de sentidos e práticas que envolvem o tema, desde a síntese das primeiras anfetaminas em laboratório, no início do século XX, até o momento atual, em que o metilfenidato é reconhecido como principal via de tratamento do TDAH, alcançando altíssimas taxas de consumo ao redor do planeta. Por fim, são apontadas algumas questões pertinentes ao contexto brasileiro, principalmente no que se refere às políticas públicas de saúde.

Resumen El metilfenidato, la principal sustancia usada en el tratamiento farmacológico del Trastorno de Déficit de Atención e Hiperactividad (TDAH), es actualmente el psicoestimulante más consumido en el mundo y tema constante en los medios de comunicación y en la producción científica de psicología y psiquiatría. En este artículo, se discuten algunos elementos del discurso científico sobre este producto, utilizándose elementos históricos, ricos en controversia, para proponer su emergencia como un problema, como indicado por Foucault. De este modo, se analiza la diversidad de significados y prácticas que implican el tema, desde la síntesis de las primeras anfetaminas en laboratorio, a principios del siglo XX, hasta el momento presente, donde el metilfenidato es reconocido como el principal medio de tratamiento del TDAH, alcanzando tasas de consumo extremadamente altas en todo el mundo. Por último, señalamos algunas cuestiones relacionadas con el contexto brasileño, especialmente con respecto a las políticas de salud pública.

Abstract Methylphenidate, the main substance used in the pharmacological treatment of Attention Deficit Hyperactivity Disorder (ADHD), is currently the most consumed psychostimulant in the world and a constant matter in media and scientific production in psychology and psychiatry studies. In this article, we discuss some scientific discourse elements about this medicine by using historical elements that are rich in controversies, in order to propose their emergence as a problem, as Foucault indicates. Thus, we have analysed the diversity of meanings and practices involving this issue, from the production of the first amphetamines in laboratory in the early twentieth century to the present days, in which methylphenidate is recognized as the first choice of treatment for ADHD, reaching extremely high consumption rates around the planet. Finally, some relevant questions about the Brazilian context are pointed out, especially concerning public health policies.

Changes of Heart Rate Variability during Methylphenidate Treatment in Attention-Deficit Hyperactivity Disorder Children: A 12-Week Prospective Study

PURPOSE: The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. MATERIALS AND METHODS: Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. RESULTS: Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. CONCLUSION: The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.

Caffeine and physical training: effects on cardiac morphology and cardiovascular response / Cafeína e treinamento físico: efeitos na morfologia cardíaca e respostas cardiovasculares

Objective to analyze the morphological structure of cardiac, blood pressure (BP), heart rate (HR) and heart rate variability (HRV) of rats subjected to physical training with supplementation of caffeine. Methods 60 rats were divided into 4 groups: control (CO), control with caffeine (CAF), trained control (TRE) and trained with caffeine (TCAF). All trained groups underwent 4 weeks of swimming, and all caffeine groups were supplemented by voluntary ingestion of caffeine diluted in drinking water. Results there were no changes to BP and HR between groups. Regarding HRV, there was a decrease in LFnorm (low frequency) and LF/HF ratio (low and high frequency) in TCAF and CAF compared to group (p<0.02 and p<0.03, respectively). An increase occurred in CAF compared to the CO in the component LFnorm (p<0.05). The results also showed an increase in the relative weight of heart in the TRE (p<0.04) and TCAF (p<0.03) compared to CO. Conclusion caffeine did not modify the hemodynamic responses. However, physical training resulted in a decrease in sympathetic response and an increase in relative heart weight. .

Objetivo analisar a histologia cardíaca, a pressão arterial (PA), a frequência cardíaca (FC) e a variabilidade da frequência cardíaca (VFC) de ratos submetidos a treinamento físico e suplementação de cafeína. Métodos sessenta ratos foram divididos em grupos controle (CO), controle suplementado com cafeína (CAF), treinados controle (TRE) e treinados suplementados com cafeína (TCAF). Os grupos de treinamento realizaram natação por quatro semanas, e os grupos de cafeína foram suplementados por ingestão voluntária de cafeína diluída em água. Resultados não houve modificações para PA e FC entre os grupos. Em relação à VFC, houve diminuição nos componentes LFnorm (baixa frequência) e LF/HF (razão baixa e alta frequência) em TCAF em relação a CAF (p<0,02 e p<0,03, respectivamente). Houve também aumento em CAF em relação a CO no componente LFnorm (p<0,05). Os resultados também mostraram aumento no peso relativo do coração em TRE (p<0,04) e TCAF (p<0,03) em relação a CO. Conclusão a cafeína não modificou as respostas hemodinâmicas. Entretanto, a natação diminuiu a resposta simpática e aumentou o peso relativo do coração. .

El dilema del metilfenidato en el TDAH: estudio de caso / The dilema of methylphenidate in the ADHD: case of study

El Trastorno por Déficit de Atención con Hiperactividad (TDAH), es una de las alteraciones del neurodesarrollo de mayor prevalencia; su trinomio sintomático de desatención, hiperactividad e impulsividad, genera significativas dificultades en distintos contextos en donde se desenvuelve el niño. Este trabajo presenta el estudio de caso de un niño de 11 años, diagnosticado con TDAH con predominio de déficit de atención (TDAH-DA), medicado con metilfenidato (MFD) a 36 mg. Se buscó analizar y comparar las diferencias en el desempeño de atención y funciones ejecutivas, evaluadas a través de la batería neuropsicológica Monitoreo Cognitivo Computarizado, en relación a la presencia o ausencia de medicación. Los resultados permiten evidenciar como la suspensión de la mediación en este caso afectó el sistema pre-atencional, la atención sostenida y la flexibilidad cognitiva, y no así la atención selectiva, la fluencia de lectura, la capacidad de nominación y el output motor, en especial de la mano izquierda, los cuales incluso obtuvieron un mejor desempeño al suspenderla. Este estudio plantea los beneficios del MFD en el sistema pre-atencional y atención sostenida más que en la atención selectiva y su influencia en el detrimento de la velocidad de procesamiento.

The Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders. Its symptomatic trinomial of inattention, hyperactivity and impulsiveness generates significant difficulties within several contexts in which the child evolves. This work shows a case study of an 11-yearoldboy, diagnosed with ADHD subtype: inattentive, medicated with methylphenidate (MPH) 36mg. The aim of this study was to analyze and compare the differences regarding the development of attention and executive functions, assessed through the neuropsychological battery Cognitive Computerized Monitoring related with the presence or absence of medication. In this case, the results show how withdrawing the medication affects the pre-attentional system, sustained attention and cognitive flexibility. On the other hand, the results demonstrate that the cessation of medication does not affect selective attention, Reading fluency, naming capacity and motor output, especially the right hand’s motor output that even showed better performance when suspending medication. This study confirms the benefits of MPH in the pre-attentional system and sustained attention, more than selective attention and its influence in the detriment of processing speed.

Central nervous system stimulant actions of Alpinia galanga (L.) rhizome: A preliminary study.

Methanolic and ethyl acetate extract of A. galanga showed significant central nervous system (CNS) stimulant activity in mice using actophotometer and rotarod test. CNS stimulation at a dose of 500 mg/kg was comparable with standard drugs caffeine and amphetamine derivative modalart. The extracts did not shown any depressant effect in forced swim or tail suspension tests. It can be concluded that A. galanga rhizome may have stimulant activity in mice and the active constituents responsible for this effect is present both in crude methanolic extract as well as in ethyl acetate fraction of methanolic extract of this plant species.

Use of methylphenidate among medical students: a systematic review / Uso de metilfenidato entre estudantes de medicina: revisão sistemática

OBJECTIVE: To review the effects of methylphenidate on cognitive enhancement, memory, and performance in medical students. METHODS: A review of four databases (LILACS, PubMed, ScienceDirect, and SciELO), analyzing the title and of all articles published between 1990 and 2012 in English, Portuguese, and Spanish. Selected articles were read in entirety, including in the review those that met the established criteria. RESULTS: The prevalence of use among medical students reached 16%, with no gender difference. Most students began using the drug after entering the university, and the reasons cited to justify it are related to enhancing academic performance. CONCLUSION: There is no evidence in the literature that the use of methylphenidate is beneficial in terms of memory or learning. The drug simply increases wakefulness and alertness, reducing the time of sleep.

OBJETIVO: Revisar o uso de metilfenidato em estudantes de medicina hígidos, abordando a prevalência, variáveis demográficas, motivos e possível melhora do desempenho acadêmico desta população. MÉTODOS: Realizou-se uma revisão nas bases de dados LILACS, PubMed, ScienceDirect e Sci-ELO, analisando-se o título e resumo de todos os artigos publicados entre 1990 e 2012 nos idiomas inglês, português e espanhol. Os artigos selecionados foram lidos de forma integral, incluindo-se na revisão aqueles que atenderam aos critérios determinados. RESULTADOS: A prevalência do uso em estudantes de medicina chega a 16%, não havendo diferença entre os gêneros. A maioria dos alunos iniciou o uso após ingresso no nível superior e os motivos citados para justificá-lo estão relacionados à melhora do desempenho acadêmico. CONCLUSÃO: Não existe evidência na literatura contemporânea que o uso de metilfenidato é benéfico em relação à memória ou aprendizagem. A droga apenas torna o usuário mais desperto e alerta, reduzindo o tempo de sono.

Utilización de resonancia magnética funcional 3T para evaluar los efectos del metilfenidato sobre la función de atención en pacientes con déficit atencional / Using 3T functional magnetic resonance imaging to assess attention in patients with clinically diagnosed attention-deficit disorder before and after methylphenidate administration: assessment of drug effects on attentional function

Our objective was to assess the level of attention in patients with attention-deficit disorder using functional MRI by comparing test results before and after the use of methylphenidate. We studied 6 pediatric patients and 2 adults. All of them were subject to a attention test before and after methylphenidate administration. The pediatric patient population showed a positive difference, with higher levels of attention in the methylphenidate group. In the adult group, improvement in the attentional function was observed in one of them. This method allowed us to physiologically assess if improvement in attentional function occurred after methylphenidate administration. Therefore, this technique is viewed as an important tool for evaluating the usefulness of treatment for attention-deficit.hyperactivity disorder.

El objetivo es evaluar el nivel de atención utilizando resonancia funcional en pacientes con déficit atencional, comparando los resultados entre los test de atención realizados antes y después del uso de metilfenidato. Se estudiaron 6 pacientes pediátricos y 2 adultos. Cada uno realizó un test de atención antes y después de usar metilfenidato. El estudio grupal de los pacientes pediátricos mostró una diferencia positiva con mayor nivel de atención en el grupo con tratamiento con metilfenidato. En el test realizado con medicamento en los adultos se evidenció mejoría en la función de atención en uno de ellos. Este método permite medir fisiológicamente si existe mejoría en la función de atención después de la utilización de metilfenidato, constituyendo una herramienta para evaluar la utilidad del tratamiento del déficit atencional.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip), methamphetamine (7 mg/kg, ip), or modafinil (100 mg/kg, ip) subsequent to paradoxical sleep deprivation (PSD) for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group) that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01). Regarding slow wave sleep (SWS), rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection) in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05). In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05). Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

Efeito do metilfenidato no processamento auditivo em crianças e adolescentes com transtorno do deficit de atenção/hiperatividade / Effects of methylphenidate in auditory processing evaluation of children and adolescents with attention deficit hyperactivity disorder

OBJETIVO: Comparar o desempenho em teste de avaliação do processamento auditivo (PA) num grupo de crianças e adolescentes com transtorno do déficit de atenção e hiperatividade (TDAH) pré e pós-metilfenidato. MÉTODO: Foram aplicados testes comportamentais padronizados de avaliação do PA em 29 indivíduos com TDAH na faixa etária de 7 a 15 anos, de ambos os sexos. Utilizou-se um grupo de comparação de 29 indivíduos sem déficit de atenção, com e sem transtornos de aprendizado. RESULTADOS: O grupo com TDAH apresentou desempenho nos testes de PA semelhante ao grupo controle sem transtornos do aprendizado sendo seus resultados ainda melhores na ocasião pós-medicação. O grupo sem déficit de atenção e com problemas de aprendizagem apresentou o pior desempenho nos testes de PA e o grupo sem déficit de atenção e sem problemas de aprendizagem foi o que apresentou o melhor desempenho. CONCLUSÃO: O teste de PA não permitiu diferenciar portadores de TDAH de controles pareados; o metilfenidato se associou a melhora do desempenho nos testes de PA nos portadores de TDAH.

PURPOSE: To compare the performance of a group of children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) pre and post-methylphenidate use in a behavioral auditory processing test battery (AP). METHOD: Twenty-nine subjects, male and female, ranging from 7 to 15 years old have undergone different behavioral auditory processing tests. A control group composed of 29 subjects with and without learning disabilities was also evaluated. RESULTS: The group with ADHD had a performance similar to the control group without learning disabilities which improved after medication. The group with learning disabilities and without ADHD had the worst performance in tests while the group without learning disabilities and without ADHD exhibited the best ones. CONCLUSION: The AP battery was unable to distinguish ADHD patients from paired controls; the use of methylphenidate improved the performance on AP tests of ADHD group in the post-medication evaluation.

Modulation by caffeine of calcium-release microdomains in frog skeletal muscle fibers

The effects of caffeine on the process of excitation-contraction coupling in amphibian skeletal muscle fibers were investigated using the confocal spot detection technique. This method permits to carefully discriminate between caffeine effects on the primary sources of Ca2+ release at the Z-lines where the triads are located and secondary actions on other potential Ca Release sources. Our results demonstrate that 0.5 mM caffeine potentiates and prolongs localized action-potential evoked Ca2+ transients recorded at the level of the Z-lines, but that 1mM only prolongs them. The effects at both doses are reversible. At the level of the M-line, localized Ca2+ transients displayed more variability in the presence of 1 mM caffeine than in control conditions. At this dose of caffeine, extra-junctional sources of Ca2+ release also were observed occasionally.

Avaliação do efeito da cafeína no teste vestibular / Evaluation of the caffeine effect in the vestibular test

Há controvérsias sobre a interferência da cafeína no teste vestibular. O café é a fonte mais rica em cafeína. Enquanto em alguns serviços os pacientes são orientados a suspender a ingestão de café 24 a 48 horas antes da realização do teste, outros não consideram necessária a suspensão da ingestão dessa bebida. OBJETIVO: Avaliar o efeito da cafeína no resultado do teste vestibular. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: Estudo comparativo, transversal, pareado. O teste vestibular foi realizado em duplicidade, com intervalo máximo de cinco dias entre um e outro exame. No primeiro teste, os pacientes foram orientados a não ingerir café 24 horas antes do exame; no segundo teste, os pacientes foram orientados a beber café como de costume. Todos os participantes tinham indicação clínica de se submeter ao teste vestibular e tinham o hábito de tomar café. RESULTADOS: Participaram do estudo 19 mulheres com idade média de 49,5 anos. O consumo médio de café foi de três xícaras por dia. As queixas de ansiedade e cefaléia foram associadas ao teste realizado com suspensão do café. Não houve diferença estatisticamente significante nos resultados dos exames realizados com e sem ingestão de café. CONCLUSÃO: A ingestão moderada de café não interferiu no resultado do teste vestibular. Considerando ser recomendável que o paciente esteja tranqüilo ao se submeter ao teste vestibular e que a meia-vida da cafeína é de apenas seis horas, sugerimos que a orientação para a suspensão súbita e completa da ingestão moderada de café antes do teste vestibular para os indivíduos habituados à ingestão diária seja reavaliada.

Exist controversy about the interference of the caffeine in the vestibular test. Coffee is the richest source of caffeine. While in some services, the patients were orient to suspend the ingestion of caffeine 24 to 48 hours before the vestibular test, other not consider the suspension of this drink necessary. AIM: To evaluate the effect of caffeine in the vestibular test result. STUDY DESIGN: clinical with transversal cohort. MATERIAL AND METHOD: Seccional and matched research. The vestibular test was performed twice in the same patient, with five days interval between the exams. In the first test, the patient did not drink coffee 24 hours before the exam; in the second, the patient drunk coffee as usual. All of the participants had clinical indication for vestibular test and were used to drinking coffee. RESULTS: Nineteen women, medium age of 49,5 years, participated. The average coffee consumption was three cups per day. The complaints of anxiety and headache were associated with the submission to the vestibular test without coffee. The exams were not statistically different comparing the results of the tests performed with and without the coffee ingestion. CONCLUSION: The moderate ingestion of coffee was not shown to interfere in the results of the vestibular test. Considering that it is recommended that the patient be calm to be submitted to the vestibular test and that the half-life of the caffeine is only of six hours, we suggest that the orientation of complete and abrupt drinking coffee suspension of moderate dose before the vestibular test for the individuals used to daily drinking coffee be reevaluated.

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.