Navegando por Palavras-chave "Adenosina"
Agora exibindo 1 - 10 de 10
Resultados por página
Opções de Ordenação
- ItemEmbargoAbordagem metabólica na avaliação da neuroproteção promovida pelo agonista adenosinérgico A1 no modelo de epilepsia induzida por pilocarpina(Universidade Federal de São Paulo (UNIFESP), 2009-03-25) Silva, Iara Ribeiro [UNIFESP]; Fernandes, Maria Jose da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)It is well known that the mismatch between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are frequently associated with seizure-induced neuronal damage in adult animal. This study was performed to verify if the neuroprotective effect of adenosinergic A1 receptor agonist R-Pia injected prior to pilocarpine could modulate LCGU and LCBF during status epilepticus (SE). Four groups were studied: Saline, RPia+ Saline, Pilo and R-Pia+Pilo. For the LCGU and LCBF determinations, rats were subjected to autoradiographic methods using [14C]-2-deoxyglucose and [14C]-iodoantypirine, respectively, and studied 4 hours after SE onset. Neurodegeneration was evaluated at acute, latent and chronic period by Fluorojade-B method. The results showed significant hypermetabolism in almost all studied areas of Pilo and R-Pia+Pilo group compared to control values. The R-Pia+Pilo group presented differential hypermetabolism in several regions, with less intense rates in substantia nigra pars reticulata (-67.96%, p <0.001) and dentate gyrus (-54.01%, p <0.001) compared to Pilo group. Besides, significant increases in LCBF were observed in all brain areas of the experimental groups compared to control group. The increases of LCBF was more intense in rats from R-Pia+Pilo group compared to Pilo group, and was located mainly in the hippocampal formation (p<0.05); thalamus (P < 0.05); entorhinal cortex (P < 0.05) and mammillary body (P < 0.05). These results showed that R-Pia neuroprotective effect in hippocampus, piriform cortex and basolateral amygdala, at different periods (acute, latent and chronic) demonstrated by Fluoro Jade B method was accompanied by compensatory metabolic equilibration in brain areas involved with seizures. Our quantitative autoradiographic studies show that R-Pia induces a decrease in the imbalance between glucose consumption and local blood flow during status epilepticus and this effect could represent a compensatory mechanism resulting in neuroprotection.
- ItemSomente MetadadadosAvaliação dos efeitos da hipóxia neonatal no desenvolvimento da esquizofrenia: papel do sistema adenosinérgico(Universidade Federal de São Paulo (UNIFESP), 2020-08-14) Ramos, Aline Camargo [UNIFESP]; Calzavara, Mariana Bendlin [UNIFESP]; Universidade Federal de São PauloRecently, efforts have been made in understanding the role of neurodevelopment in schizophrenia. It is believed that the manifestation of schizophrenia, reflecting the striatal hyperdopaminergic state, is the result of changes that emerge from the interaction between genetic, environmental and neurodevelopment-related factors throughout life. The pharmacotherapy of schizophrenia based on the dopaminergic hypothesis remains unsatisfactory for the treatment of negative symptoms and cognitive deficits related to this disease. Adenosine is a homeostatic modulator capable of affecting different complex networks such as neurotransmitter-dependent pathways, bioenergetics and epigenetics. In this sense, adenosine appears to be a promising candidate in correcting the functional imbalance found in schizophrenia, and may influence the dopaminergic and glutamatergic systems. Evidence points out to an important participation of adenosine in neural development and indicates a potential involvement of this substance in the etiology of schizophrenia. Perinatal hypoxia is one of the most well-established risk factors for the development of schizophrenia. However, there are few studies adressing the mechanisms related to the role of hypoxia in the pathophysiology of schizophrenia. Systems subjected to hypoxia have reported increased adenosine levels as one of the adaptive responses. Many of these effects evolve to permanent changes that are still not well understood, which may have an important role in the pathophysiology of numerous diseases, including schizophrenia. Animal and cellular models can be interesting tools for the study of interventions such as perinatal hypoxia and its repercussions on brain and behavioral function that mimic the changes observed in schizophrenia. Hence, the objective of this work was to study the effects of neonatal chemical hypoxia on the development of schizophrenia, evaluating the role of the adenosinergic system in the modulation of the dopaminergic system as a participant factor in the pathophysiology of schizophrenia. Therefore, Wistar rats were treated with cobalt chloride, a chemical hypoxiainducing compound, in the neonatal period (7 days of age). These animals were subjected to behavioral tests at young age (50 days) to assess whether they had xx behavioral changes related to the first psychotic episode. In adulthood (90 days),animals were tested in paradigms that analyze behavioral changes related to schizophrenia, such as locomotion, social interaction and context-based fear. Molecular tests were performed in samples from the brain of these animals in order to check the expression of genes related to hypoxia and also neuronal patterns. Our results showed that rats treated with cobalt chloride in the neonatal period showed behavioral changes related to schizophrenia at young and adult age compared to animals that received saline solution. These animals had increased expression of HIF-1α and VEGF and reduced immunoreactivity of parvalbuminpositive interneurons in the prefrontal cortex as adults compared to animals from the control group. We observed that the behavioral changes were reversed by the acute use of haloperidol antipsychotic and that the use of caffeine, but not selective adenosinergic antagonists, previously the administration of cobalt chloride was able to prevent the changes firstly observed. Finally, we note that the changes observed in animals that received cobalt chloride were similar to those observed in animals from the SHR strain, which is used as an animal model for the study of schizophrenia. Thus, we can suggest that chemical hypoxia in the neonatal period causes behavioral and neuronal changes related to schizophrenia in rats, reinforcing that neonatal hypoxia is a risk factor for the later development of schizophrenia. The participation of the adenosinergic system in the pathophysiology of schizophrenia is supported by the results obtained in this work, since the use of caffeine as a pretreatment was able to prevent the behavioral changes caused by chemical hypoxia. Caffeine, by antagonizing adenosine receptors, normalizes the transmission that has been altered by chemical hypoxia, indicating the importance of adequate levels of adenosine for normal neurodevelopment. Situations that alter this transmission, such as hypoxia, impair brain development and increase the risk of psychiatric disorders, such as schizophrenia.
- ItemSomente MetadadadosCaracterizacao do sistema adenosinergico no modelo experimental de epilepsia induzido por pilocarpina(Universidade Federal de São Paulo (UNIFESP), 2001) Vianna, Eduardo Paulo Morawski [UNIFESP]A adenosina e um importante modulador do sistema nervoso central, exercendo um potente efeito inibitorio na liberacao de neurotransmissores. A adenosina extracelular pode ser liberada por celulas, ou sintetizada no meio extracelular por uma enzima ancorada a membrana externa, a ecto-5'-nucleotidase. A adenosina exerce um efeito anticonvulsivante em muitos modelos experimentais, inclusive no modelo da pilocarpina. No entanto, nao se sabe que receptores estao envolvidos. Os objetivos deste trabalho foram estudar, por histoquimica, a atividade da enzima ecto-5'-nucleotidase no cerebro de ratos nos 3 periodos do modelo experimental de epilepsia induzida por pilocarpina e caracterizar o papel de cada receptor quanto a capacidade de modular as crises induzidas por pilocarpina, empregando agonistas e antagonistas de receptores A1, A2a e A3. O efeito neuroprotetor dos tratamentos tambem foi avaliado no modelo da pilocarpina. A histoquimica da ecto-5'-nucleotidase revelou um aumento na marcacao na regiao CA3 do hipocampo nos grupos 5 horas pos SE, sendo intensificado 24 horas e 7 dias apos a inducao do SE. Nos animais cronicos, a marcacao ocorreu principalmente nas fibras musgosas de CAI, evidenciando o rebrotamento. O resultado dos pre-tratamentos mostrou que os agonistas dos receptores A1 tem efeito anticonvulsivante visto que o R-PIA diminui as crises induzidas por pilocarpina, e que o seu antagonista, DPCPX, teve efeito convulsivante. O receptor A2a tambem tem efeito anticonvulsivante. Apesar do seu agonista, CGS 21680, nao modificar o curso das crises, o antagonista deste receptor teve acao convulsivante. O receptor A3 parece nao participar na modulacao das crises. No estudo de neuroprotecao, verificou-se que tanto receptores A1 quanto A2a protegem o cerebro contra a morte neuronal por apoptose. De acordo com esses resultados,. pode-se concluir que: o SE induzido pela pilocarpina causa um aumento da ecto-5'-nucleotidase, indicando um aumento da concentracao de adenosina extracelular no hipocampo no modelo estudado. Os receptores A1 e A2a tem efeitos anticonvulsivante e neuroprotetor. Entretanto, o recepto A3 pode contribuir para a morte neuronal por apoptose
- ItemAcesso aberto (Open Access)Contribuição da adenosina para o papel antiepileptogênico da estimulação cerebral profunda no núcleo anterior do tálamo(Universidade Federal de São Paulo, 2023-11-13) Ball, Christiane Gimenes [UNIFESP]; Covolan, Luciene [UNIFESP]; Malheiros, Jackeline Moraes [UNIFESP]; http://lattes.cnpq.br/0231673027524958; http://lattes.cnpq.br/4322693242221219; http://lattes.cnpq.br/8123236192117783O objetivo do estudo é determinar o efeito do ANT-DBS (Anterior nucleus of the thalamus-Deep brain stimulation) durante a epileptogênese usando o modelo de kindling por pentilenotetrazol (PTZ) em ratos. Para isso, foram executados 2 estudos paralelos para determinação do [1] perfil da epileptogênese e suas consequências comportamentais no kindling por PTZ em ratos machos e fêmeas e [2] efeitos do ANT-DBS durante o kindling, avaliando a participação do sistema adenosina quinase (ADK)/adenosina (ADO) como possível mediador do efeito antiepileptogênico. Nos 2 estudos o kindling foi induzido por injeções de PTZ (30 mg/kg ip) 3 dias por semana, durante 6 semanas. No estudo 1, ratos machos (n = 10) e fêmeas (n = 11) foram avaliados quanto aos escores de crises durante o kindling e ao final, testados para memória de curto e longo prazo. O estudo 2, utilizou 79 ratos machos separados em 3 grupos: PTZ (n = 26), PTZ-DBS (n = 28) e PTZ-sham (n = 25). O ANT-DBS (130 Hz, 90 μs e 200 μA) foi realizado pareado com injeções de PTZ. Ao final do kindling um subgrupo desses animais foi sacrificado para extração do cérebro para estudar a expressão de ADK. Para observar possíveis efeitos duradouros da estimulação no núcleo anterior do tálamo, o outro subgrupo de animais permaneceu 1 semana livre de estimulação antes de receberem nova dose de PTZ (desafio). No estudo 2 também foi avaliado o escore de crises entre os grupos. As conclusões do estudo 1 indicaram que as fêmeas apresentam menor suscetibilidade a crises durante o kindling por PTZ e que a memória de longo prazo é muito afetada em ambos os sexos, enquanto a memória de curto prazo é afetada principalmente no sexo feminino. A suscetibilidade às crises não se correlacionou com o ciclo estral, nem com a perda de memória, mas o comprometimento da memória teve forte correlação com a contagem de células hipocampais. O estudo 2 demonstrou que o ANT-DBS suprime as crises durante o kindling e que essa supressão é duradoura uma vez que seus efeitos permanecem mesmo após um período de 1 semana sem estimulação. A análise do tecido hipocampal desses animais indica uma redução na expressão da ADK no grupo PTZ-DBS o que sugere um aumento da disponibilidade local de ADO, compatível com seu efeito antiepiléptico.
- ItemAcesso aberto (Open Access)Efeito da adenosina na proliferação e apoptose das células do intestino delgado de ratos submetidos à isquemia e reperfusão intestinal(Universidade Federal de São Paulo, 2024-10-10) Oliveira, Jefferson Vilela de [UNIFESP]; Taha, Murched Omar [UNIFESP]; Rodrigues, Francisco Sandro Menezes [UNIFESP]; http://lattes.cnpq.br/4697952451041850; http://lattes.cnpq.br/5780852783167227; http://lattes.cnpq.br/1948921887755990Objetivo: Estudar o efeito da adenosina na proliferação e apoptose das células do intestino delgado de ratos submetidos à isquemia e reperfusão intestinal. Método: foram utilizados 30 ratos machos adultos, com 250 a 300 g da linhagem EPM-1 Wistar, distribuídos em 5 grupos, de 6 animais por grupo: GI: Sham; GII isquemia intestinal (II) com solução salina (SS); GIII isquemia e reperfusão intestinal (iIR) com SS; GIV (II) com adenosina e GV iIR com adenosina. A SS e a adenosina (45mg/kg) foram aplicadas pela veia femoral, nos grupos de iI 5 min antes da sua realização. A artéria mesentérica superior foi clampeada por 60 min para proporcionar iI. A SS e de adenosina foram infundidas nos animais de seus respectivos grupos pela veia femoral, 5 min antes de realizar a iI. Nos Grupos iI/R, as soluções foram infundidas 5 min antes da isquemia, e 5 min antes da iR e aos 55 minutos após a i/R. O tempo total de i/R foi de 60 min. Ao final do procedimento, retirou-se segmento do intestino delgado (jejuno) de cada animal para a realização do estudo da proliferação celular e da expressão de apoptose. Foi utilizado o Teste de (ANOVA) complementado pelo teste de Tukey (“Grafpad 5 Prisma”) (p<0,05). Resultados: A adenosina mostrou-se eficiente na preservação do intestino delgado submetido tanto a isquemia isolada quanto a isquemia seguida de reperfusão. Em relação a proliferação celular, que ocorre somente nas glândulas intestinais, essa proteção mostrou ser 42% no grupo III (I+AD) e de 38% no grupo IV na proliferação celular. Em relação a apoptose notamos haver maior intensidade nas vilosidades intestinais sendo que a adenosina ofereceu proteção ao redor de 50% no grupo III (I+AD) e de 70% no grupo IV (i/R+AD). Conclusões: Os dados mostraram que a adenosina foi capaz de gerar citoproteção tanto no que se refere à proliferação celular quanto à apoptose do intestino delgado de ratos submetidos a isquemia e reperfusão.
- ItemSomente MetadadadosEfeitos da Adenosina e do Precondicionamento Isquemico na(Universidade Federal de São Paulo (UNIFESP), 2010) Haddad, Mauro Assi [UNIFESP]
- ItemAcesso aberto (Open Access)Estudo do bloqueio do receptor adenosinérgico A2A no modelo experimental de epilepsia induzida por pilocarpina(Universidade Federal de São Paulo (UNIFESP), 2009-05-27) Rosim, Fernanda Elisa [UNIFESP]; Fernandes, Maria Jose da Silva [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Adenosine is an important endogenous neuromodulator with anticonvulsant and neuroprotective properties. The present work studied the effect of blocking the adenosinergic A2A receptor by selective antagonist SCH58261, associated or not, the activation of A1 receptor by agonist R-Pia in the seizures modulation and neuroprotection of the brain areas vulnerable to injury in the pilocarpine model. Eight groups were studied: Pilo, SCH+Pilo, RPia+ Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, RPia+ SCH+Saline. The behavioral parameters: number of animals that developed status epilepticus, latency to the beginning of SE and mortality rate after the insult were evaluated. Through the technique of FJ-B, evaluated the neurodegeneration and through the technique of immunohistochemistry, the caspase -1 expression in brain regions, 24 hours and 7 days after SE. The results showed that pre-treatment with SCH58261, R-Pia and the combination of both reduced the number of animals in SE, increased the threshold for the establishment of the SE and decreased the mortality rate after the insult, compared to pilocarpine treatment. The pre-treatment with R-Pia e R-Pia + SCH58261 reduces the intensity of marking by FJ-B in CA3, hilus of dentate gyrus and piriform cortex after 24 hours and 7 days of the SE, compared to pilocarpine treatment. The caspase -1 expression, 24 hours after the SE, was intense in the amygdala, and moderate in the piriform and entohrinal cortex and absent in the hippocampus, whereas, 7 days after SE, the expression was intense in the hippocampus and amygdala, discreet in the cortex entohrinal and moderate in the piriform cortex in all groups, except in the controls. We conclude that the A2A antagonist have potent anticonvulsant effect, but does not promote neuroprotection in brain areas vulnerable to injury, while the A1 agonist, has a crucial role in the modulation of seizures and promotes significant neuroprotection in the pilocarpine model.
- ItemAcesso aberto (Open Access)Papel dos receptores de adenosina e da PKA no prejuízo de memória causado pela privação de sono(Universidade Federal de São Paulo (UNIFESP), 2017-12-20) Oliveira, Sophia La Banca de [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; http://lattes.cnpq.br/6303382961871353; http://lattes.cnpq.br/7411925710894750; Universidade Federal de São Paulo (UNIFESP)Sleep deprivation (SD) impairs various cognitive functions, including different types of memory. Various neurotransmitters and neuromodulators signaling pathways are altered by SD, including adenosine signaling. Adenosine is a neuromodulator which acts as the main homeostatic regulator of sleep, its extracellular concentrations raise in various regions of the brain during SD. The behavioral effects of adenosine are dependent mainly on its actions on two receptors, the A1, a Gi protein coupled receptor, and A2A, a Gs protein coupled receptor. A1 receptor activation impairs memory formation, while the role of A2A receptor on memory formation is not well understood yet. Among the main intracellular signaling pathways modulated by adenosine are the protein kinase A (PKA) pathway and the exchange protein activated by cAMP (EPAC) pathway. Both enzimes are involved on the induction of long term potentiation (LTP), a cellular correlate of memory. Considering this background we suggest that adenosine has an important role in the memory impairment caused by SD through the activation of the adenosine receptors on the brain regions recruited during memory formation, such as the hippocampus and the striatum, and by consequent modulation of the PKA and EPAC pathways. To test this hypothesis we first evaluated the effect of 96 hours of SD through the multiple platform modified method on the levels of the A1 and A2A receptors on the hippocampus. We also used the phosphorylation of PKA to infer its activity. We observed that sleep deprivation decreased the levels of A2A receptor and phosphorylation of PKA, but had no effect on the A1 receptor levels. Then we tested the effect of DPCPX, an antagonist of the A1 receptor, on the performance of sleep deprived animals on two memory tasks, the multiple trial inhibitory avoidance (MTIA) and the contextual fear conditioning (CFC), and the effect of an A2A agonist, CGS 21680, and an A2A antagonist, ZM 241385, on the MTIA. The results showed that DPCPX prevented the impairment on the performance on the MTIA, but not on the CFC. While CGS 21680 had no effect on the performance on the MTIA, ZM 241385 impaired the xix performance of the control animals and increased the performance of the sleep deprived animals. We also tested the effect of SD and DPCPX on the levels of the A1 receptors in the phosphorylation of PKA and activation of EPAC in the striatum and hippocampus after the training session of the MTIA. SD increased the levels of A1 receptor on the striatum, but not in the hippocampus, DPCPX had no effect on neither structures. SD decreased PKA phosphorylation on both structures, DPCPX prevented this effect on the striatum, but not on the hippocampus. SD had no effect on the activity of EPAC. Finally, we tested the effect of drugs which act on other neurotransmitter systems on the phosphorylation of PKA on the hippocampus of animals subjected to the training session of the MTIA. We replicated the result that indicated a decrease on PKA phosphorylation and reverted it with the administration of d-ciclosserin, a NMDA coagonist. The alteration on the level of A2A receptors on the hippocampus and A1 receptors in the striatum indicates that SD has an impact on adenosine signaling on both structures. The activation of PKA on the hippocampus in the time interval between 30 minutes and 6 hours after the MTIA training session is necessary for memory consolidation. Its activation is also necessary for the LTP formation in the striatum. Thus, the decrease of the phosphorylation on these structures caused by SD after the MTIA training may be related to the effects of SD on memory. MTIA task has an instrumental component on which structures of the striatum are involved, this does not happen on the CFC, thus the effect of DPCPX on the MTIA, but not on the CFC may be related to the A1 receptors on the striatum, but not on the hippocampus. This result, as well as the increase on the levels of A1 receptors and the reversion of the decrease of PKA phosphorylation on the striatum indicate that the A1 receptors on the striatum have an important role on the performance impairment on MTIA caused by SD. On the other hand, DPCPX did not prevent the impairment on the CFC nor the decrease of the phosphorylation of PKA on the hippocampus, indicating that another neurotransmitter system would be involved on the impairment on this task. The reversion of the decrease of phosphorylation caused by the dciclosserin suggests an involviment of the NMDA receptors.
- ItemSomente MetadadadosParticipação Do Ampc Extracelular Na Regulação Da Transmissão Neuromuscular Esquelética(Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Duarte, Thiago [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: In skeletal muscle, the intracellular cyclic AMP regulates processes that include the contraction, metabolism, and expression of synaptic proteins (Duarte et al., 2001; Bergantin et al. 2011). Studies of our group have shown that after the activation of GsPCR or adenylyl cyclase, part of the newly formed intracellular cAMP is transported to the cellular interstitium (Godinho and Costa-Jr 2003; Chiavegatti et al., 2008). The cAMP is able to act as an extracellular signaling molecule through its metabolite adenosine, formed by the sequential action of ecto-phosphodiesterases and ecto-5'-nucleotidases (Chiavegatti et al., 2008). More recently, we have demonstrated that β2 adrenoceptor activation has a biphasic action characterized by the initial potentiation of muscle contraction resulting from the increase of intracellular cAMP, followed by a negative inotropic effect, related to cAMP efflux and activation of A1 receptors by the adenosine metabolite (Duarte et al, 2012). It is known that adenosine formed from ATP released by the motor neuron is able to modulate neuromuscular transmission through its adenosine metabolite and activation of neuronal adenosine receptors (Ribeiro J.A, et al., 1996), but in skeletal muscle, It was not identified whether the efflux and metabolism of cAMP, regulates the neuromuscular transmission Objective: Evaluate the participation of extracellular cAMP and its metabolite adenosine in neuromuscular transmission. Methods: Male diaphragm muscles were used for 3 to 4 months, and muscle contraction was induced by electrical stimulation of the phrenic nerve (n = 3-4). The train-of-four TOF electrical stimulation protocol (2 Hz, 2 ms duration) was used and the ratio between the contraction amplitude of the fourth (T4) and the first stimulus (T1) was determined to evaluate the effect of the neuromuscular blockers d-tubocurarine and hexamethonium in the presence or absence of cAMP, clenbuterol and / or formoterol, with or without preincubation of adenosine receptor antagonists (CGS15943 and ZM241385) or inhibitors of organic anion (probenecid) ecto-5'-nucleotidase (AMPCP). The effect of formoterol on intra- and extracellular cAMP was quantified by time resolving-FRET assay.Results: 300 nM d-tubocurarine and 1.5 mM hexamethonium caused 25% neuromuscular block, this effect was inhibited by the 30 min preincubation with 100 μM cAMP and by the agonists of β2adenoceptors 100 nM clenbuterol and 100 nM formoterol which also promoted a 15% increase in contraction force, these effects were associated with increased of intracellular and extracellular cAMP levels. The adenosine receptor antagonists 100 nM CGS15943 (non-selective) and 100 nM ZM241385 (A2A selective) and the inhibitors of organic anion (300 μM probenecid) and ecto-5'-nucleotidase (100 μM AMPCP) inhibited the effect cAMP and clenbuterol on d-tubocurarine and hexamethonium-induced tetanic fade. Conclusions: The results presented in this work show that the extracellular cAMP adenosine pathway initiated by activation of post-synaptic β2 adrenoceptors modulates the contraction of skeletal muscle induced by phrenic nerve stimulation. These modulations depend on efflux of cAMP and activation of presynaptic adenosine receptors and probably involve increment in ACh release. However, this pathway can act as a paracrine signaling that creates feedback loop and regulation between muscle fibers and motor neurons.
- ItemSomente MetadadadosUso de modelos experimentais para a determinação da ação ansiolítica de fármacos: um estudo com a carbamazepina(Universidade Federal de São Paulo (UNIFESP), 2002) Leite, Jose Roberto [UNIFESP]Introdução: A carbamazepina, um farmaco utilizado principalmente por sua atividade antiepileptica, apresenta outros efeitos terapeuticos em alguns transtornos psiquiatricos, principalmente nos transtornos de humor. Relatos clinicos tambem sugerem efeito ansiolitico para esse medicamento. Como mecanismo de acao desse farmaco, alem das evidencias propondo que o mesmo atua em canais ionicos, outras sugerem efeitos em sistemas de neurotransmissao e em particular no sistema do adenosina. Objetivos: Estudar, utilizando-se de modelos experimentais, um possivel efeito ansiolitico para o farmaco. Foram compilados alguns trabalhos por nos publicados, e que se referem ao uso de modelos experimentais em animais de laboratorio e na especie humana. Experimentos e Discussao: No primeiro e segundo experimentos, empregando-se modelo de conflito induzido por punicao de uma resposta operante, constatou-se que a carbamazepina, em doses de cinco, dez ou vinte miligramos por quilo, apresenta efeito semelhante ao do diazepam, o que sugere atividade ansiolitica. Nao se observou tolerancia a esse efeito, uma vez que o mesmo se manteve apos administracao do farmaco por um periodo de ate dez dias consecutivos. Alem disso, os resultados sugerem que o efeito observado poderia ser resultante da acao do farmaco no sistema de neurotransmissao por adenosina uma vez que seus efeitos foram antagonizados por uma baixa dose de aminofilina e potenciados pela papaverina. No terceiro experimento utilizou-se o modelo de labirinto em cruz elevado, com o objetivo de se confirmar, com o uso de um modelo no qual nao envolve condicionamento ou punicao, o efeito ansiolitico da carbamazepina. Tambem foi objetivo, avaliar o possivel papel do sistema de neurotransmissao por adenosina nesse efeito, utilizando-se de drogas que afetam esse sistema. Os resultados obtidos confirmam a acao ansiolitica e sugerem que essa atividade e mediada pela atuacao...(au)