Diss. (sammanfattning) Göteborg : Univ., 2009. / Härtill 3 uppsatser.

Made available in DSpace on 2015-07-22T20:50:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-01-01 / No processo da sensibilização comportamental, que se desenvolve a algumas drogas psicoativas, participam diversos sistemas de neurotransmissão, entre eles o sistema colinérgico, que modula de maneira importante o funcionamento de vias dopaminérgicas. Neste estudo avaliamos os efeitos da escopolamina, um antagonista colinérgico muscarínico, no desenvolvimento e expressão da sensibilização ao efeito estimulante do etanol (Estudo I) e os níveis de ligação dos receptores colinérgicos muscarínicos M1 em animais classificados como apresentando Alta (AS) ou Baixa Sensibilização (BS) ao efeito estimulante do etanol (Estudo II). No Estudo I, quatro grupos camundongos suíços albinos machos receberam durante 21 dias, respectivamente: salina+salina (sal/sal); 1,0 mg/kg de escopolamina+salina (escop/sal); salina+2,2 g/kg de etanol (sal/2,2EtOH) ou 1,0 mg/kg escopolamina+2,2 g/kg de etanol (escop/2,2EtOH). A atividade locomotora dos animais foi registrada por 20 minutos no 1°, 7°, 14° e 21° dias de tratamento. Agudamente, tanto etanol como escopolamina não alteraram a atividade locomotora dos animais, porém, a co-administração das duas drogas induziu um significativo efeito depressor, ao qual se desenvolveu tolerância com o tratamento. Apenas o grupo sal/2,2EtOH desenvolveu sensibilização. Após o tratamento foram realizados 3 desafios (28°, 31° e 34° dias), nos quais metade do grupo sal/sal recebeu salina e a outra metade recebeu a droga-desafio (etanol nos desafios 1 e 2 e escopolamina no desafio 3). Nos desafios 1 e 3, realizados nas caixas de atividade, somente os animais dos grupos sal/2,2EtOH e escop/2,2EtOH expressaram sensibilização, sugerindo "sensibilização cruzada" entre etanol e escopolamina. No desafio 2, realizado em um ambiente novo para eles (campo aberto), a expressão da sensibilização foi bloqueada. No Estudo II os camundongos foram tratados por 21 dias com salina ou 2,2 g/kg de etanol (i.p.), sendo estes classificados como AS ou BS, com base na atividade do 21° dia. Os animais foram sacrificados para análise auto-radiográfica da densidade de receptores M1, não tendo sido observadas diferenças significativas entre os animais classificados como AS, BS ou controles (salina), em nenhuma das 20 regiões encefálicas analisadas. Em resumo, a escopolamina influenciou o processo de sensibilização ao efeito estimulante do etanol, sugerindo que o sistema colinérgico é importante neste processo. Porém, as neuroadaptações que ocorreram com o tratamento crônico com etanol parecem não afetar os níveis de receptores M1. / Various neurotransmission systems have influence on the behavioral sensitization process developed after repeated administration of some drugs of abuse, among them the cholinergic system, which modulates the dopaminergic pathway’s functioning. In this study we evaluated the influence of scopolamine (an antagonist of cholinergic muscarinic receptors) on the development and _expression of behavioral sensitization to ethanol (Study I), as well as on the M1 binding, in animals classified as presenting high (AS) or low (BS) sensitization to ethanol (Study II). In Study I, four groups of male Swiss albino mice received one of the following during 21 days: saline+saline (sal/sal); 1.0 mg/kg of scopolamine+saline (escop/sal); salina+2.2 g/kg of ethanol (sal/2.2EtOH) or 1.0 mg/kg scopolamine+2.2 g/kg of ethanol (escop/2.2EtOH). Their locomotor activity was recorded during 20 minutes on the first, 7th, 14th and 21st days of treatment. Acutely, neither ethanol nor scopolamine altered their locomotor activity; however the co-administration of the both drugs induced a significant depressor effect to which tolerance was developed. Only the sal/2.2EtOH group developed sensitization. After the treatment, 3 challenge tests were carried out (on days 28th, 31st and 34th), in which half of the sal/sal group received saline and the other half received the challenge drug (ethanol in challenges 1 and 2 and scopolamine in challenge 3). In challenges 1 and 3 the animals were tested in activity cages and only the sal/2.2EtOH and escop/2.2EtOH groups expressed sensitization, suggesting there is cross-sensitization between ethanol and scopolamine. In challenge 2, which was conducted in a new environment (open-field arena), the _expression of the sensitization was blocked. In Study II, mice were treated during 21 days with saline or 2.2 g/kg ethanol (i.p.) and the ethanol treated mice were classified as AS or BS, according to their locomotor activity on day 21st. The animals were sacrificed and the bindings to M1 sites were examined by auto-radiographic analyses. No significant differences were found among groups (AS, BS and control) in any of the 20 brain regions analyzed. The present results suggest that scopolamine influences the process of sensitization to ethanol and that the cholinergic system participates in this process. However, the neuroadaptation that occurred after chronic ethanol treatment does not seem to change the binding to M1. / TEDE / BV UNIFESP: Teses e dissertações

<p>Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this&nbsp / herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study&nbsp / was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats / &nbsp / and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 &mu / g/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50&nbsp / g/kg), losartan (30 mg/kg), phenylephrine (0.01 &ndash / 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 &ndash / 10.0 &mu / g/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 &mu / g/kg),&nbsp / and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5&nbsp / months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure&nbsp / transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10&nbsp / mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean&nbsp / of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student&rsquo / s t test&nbsp / for significant difference (p &lt / 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p &lt / 0.05) reduced the systolic, diastolic, and mean&nbsp / arterial BP / and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p &lt / 0.05) increased the BP, while propranolol, muscarine and&nbsp / atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent / with both increases as well as decreases observed with ang&nbsp / I, and II and atropine, while decreases were seen with muscarine. Captopril produced&nbsp / significant (p &lt / 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p &lt / 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the&nbsp / MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not&nbsp / produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin.&nbsp / The co-infusion of dobutamine with T. violacea produced siginificant (p &lt / 0.05) increases in DBP which were associated with significant (p &lt / 0.05) reductions in HR, when&nbsp / compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when&nbsp / compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to&nbsp / dose dependent significant (p &lt / 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or&nbsp / captropril produced (a) signicant (p &lt / 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced&nbsp / signifiant (p &lt / 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated&nbsp / group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study&nbsp / suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the &beta / 1&nbsp / adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also&nbsp / suggest that the MLE may not act&nbsp / through the angiotensin II receptors or the &alpha / 1 adrenergic receptors.&nbsp / </p>

<p>Tulbaghia violacea Harv. (Alliaceae) is a small bulbous herb which belongs to the family, Alliaceae, most commonly associated with onions and garlic. In South Africa (SA), this&nbsp / herb has been traditionally used in the treatment of various ailments, including fever, colds, asthma, paralysis, hypertension (HTN) and stomach problems. The aim of this study&nbsp / was to evaluate the effect of methanol leaf extracts (MLE) of T. violacea on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats / &nbsp / and to find out the mechanism(s) by which it acts. The MLE of T. violacea (5 - 150 mg/kg), angiotensin I (ang I, 3.1 - 100 &mu / g/kg), captopril (10 mg/kg), angiotensin II (ang II, 3.1 - 50&nbsp / g/kg), losartan (30 mg/kg), phenylephrine (0.01 &ndash / 0.16 mg/kg), prazosin (1 mg/kg), dobutamine (0.2 &ndash / 10.0 &mu / g/kg), propranolol (0.1 - 12.8 mg/kg), muscarine (0.16 -10 &mu / g/kg),&nbsp / and atropine (0.02 - 20.48 mg/kg) were administered intravenously into male spontaneously hypertensive rats (SHR) weighing between 300 g and 350 g and aged less than 5&nbsp / months. The MLE of T. violacea and/or the standard drugs were infused alone, simultaneously, or separately into each animal. The BP and HR were measured via a pressure&nbsp / transducer connecting the femoral artery and the Powerlab. The vehicle (0.2 mls of a mixture of dimethylsulfoxide and normal saline), T. violacea (60 mg/kg) and captopril (10&nbsp / mg/kg) were injected intraperitoneally into some SHR for 21 days to investigate the chronic effect of these agents on plasma levels of aldosterone. The mean change, the mean&nbsp / of the individual percentage changes and the percentage difference (in mean) observed with each intervention was calculated and statistically analyzed using the Student&rsquo / s t test&nbsp / for significant difference (p &lt / 0.05). The Microsoft Excel software was used for statistical analysis. T. violacea significantly (p &lt / 0.05) reduced the systolic, diastolic, and mean&nbsp / arterial BP / and HR dose-dependently. In a dose-dependent manner, ang I, ang II, phenylephrine significantly (p &lt / 0.05) increased the BP, while propranolol, muscarine and&nbsp / atropine reduced the BP. The increases in BP due to dobutamine were not dose-dependent. In a dose dependent manner, phenylephrine and propranolol reduced the HR, while dobutamine increased the HR. The effect of ang I, ang II, muscarine and atropine on HR were not dose-dependent / with both increases as well as decreases observed with ang&nbsp / I, and II and atropine, while decreases were seen with muscarine. Captopril produced&nbsp / significant (p &lt / 0.05) reduction in BP which were not associated with any change in HR. The co-infusion of ang I with the MLE produced significant (p &lt / 0.05) reduction in BP, which were not associated with significant changes in HR. The co-infusion of ang II with the&nbsp / MLE did not produce any significant changes in BP or HR when compared to the infusion of the standard drug alone. The co-infusion of phenylephrine with the MLE did not&nbsp / produce any significant change in BP or HR when compared to the values obtained with the infusion of the standard drug alone, in both the absence and presence of prazosin.&nbsp / The co-infusion of dobutamine with T. violacea produced siginificant (p &lt / 0.05) increases in DBP which were associated with significant (p &lt / 0.05) reductions in HR, when&nbsp / compared to the values obtained with the infusion of the standard drug alone. Theco-infusion of atropine with the MLE did not produce any significant change in BP or HR when&nbsp / compared to the values obtained with the infusion of atropine alone. However, the infusion of T. violacea, 20 minutes after pre-treating animals with atropine (5.12 mg/kg) lead to&nbsp / dose dependent significant (p &lt / 0.05) increases in BP, which were associated with dose-dependent increases in HR. The chronic treatment of animals with T. violacea or&nbsp / captropril produced (a) signicant (p &lt / 0.05) reductions in the plasma levels of aldosterone when compared to the values obtained in the vehicle-treated group, (b) produced&nbsp / signifiant (p &lt / 0.05) reduction in BP in the captopril treated group when compared to the vehicle-treated, (c) did not produce any signficant change in BP in the T. violacea-treated&nbsp / group when compared to the vehicle-treated group and (d) did not produce any signifiant change in HR or body weight in any of the groups. The result obtained in this study&nbsp / suggests that T. violacea reduced BP and HR in the SHR. Secondly, the BP and HR reducing effect of the MLE may involve a) the inhibition of the ACE, b) the inhibition of the &beta / 1&nbsp / adrenoceptors, c) the stimulation of the muscarinic receptors and d) the reduction of the levels of aldosternone in plasma. The results also&nbsp / suggest that the MLE may not act&nbsp / through the angiotensin II receptors or the &alpha / 1 adrenergic receptors.&nbsp / </p>

Made available in DSpace on 2015-07-22T20:49:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-31. Added 1 bitstream(s) on 2015-08-11T03:25:40Z : No. of bitstreams: 1 Publico-063.pdf: 1283927 bytes, checksum: 89787a2a88db59b03f60213385f6b0ba (MD5) / Nosso laboratório mostrou que um único gene codifica um precursor protêico, cujo processamento gera o peptídeo natriurético tipo C (CNP) e uma variedade de peptídeos ricos em prolina, conhecidos como peptideos potenciadores da bradicinina ou BPPs. Com pequenas diferenças, esse precursor é expresso na glândula do veneno e na região neuro-endócrina do cérebro da Bothrops jararaca. Todos os produtos desse processamento têm como característica comum sua ação sob o sistema cardiovascular, levando à redução da pressão arterial e da frequência cardíaca. Esse fato intrigante levou-nos a questionar se esses diferentes peptídeos teriam mecanismo de ação semelhante. Surpreendentemente, esse trabalho mostrou que a resposta é negativa embora ainda não possamos explicar detalhadamente como cada um desses peptídeos atua no complexo mecanismo responsável pelo tônus vascular e pela frequência cardíaca. Historicamente, a demonstração de que os peptídeos potenciadores da bradicinina da Bothrops jararaca (Bj-BPPs) eram inibidores naturais da enzima conversora de angiotensina (ECA) teve ampla repercussão médica. Essa inibição parecia explicar a forte ação anti-hipertensiva desses peptídeos, dai servirem de modelo estrutural para o desenvolvimento de um inibidor sítio-dirigido, o Captopril, medicamento mundialmente utilizado para o tratamento da hipertensão arterial sistêmica humana. Contudo, recentes evidências experimentais sugerem que a atividade anti-hipertensiva dos Bj-BPPs não está relacionada somente com a inibição da ECA. Nosso grupo demonstrou para o Bj-BPP-10c que sua ação anti-hipertensiva se deve à ativação da geração de L-arginina, essencial para produção de óxido nítrico, potente vasodilatador, bem como pela regulação do barorreflexo arterial e pela sinalização de cálcio intracelular, ações que contribuem para a produção de NO em células endoteliais e neurais. Outros Bj-BPPs derivados do mesmo precursor foram aqui analizados. Demonstramos que o mecanismo de ação do Bj-BPP-5a envolve receptores B2 da bradicinina, o receptor muscarínico do subtipo M1 e a produção de NO. Curiosamente, o Bj-BPP-9a que serviu de modelo para a síntese do Captopril, parece atuar predominantemente como um clássico inibidor da ECA. O Bj-BPP-11e deve ter ação num receptor de membrana, assim explicando seus efeitos sobre parâmetros cardiovasculares. O mecanismo de ação do Bj-BPP-12b poderia ser explicado pela potenciação da BK e/ou pela inbição da ECA e do Bj-BPP-13a por ação em receptor muscarínico do subtipo M3 e sobre a ASS. Adicionalmente, o presente trabalho mostrou, pela primeira vez na área de toxinologia, que toxinas de serpentes já se valem do recurso bem conhecido na geração de hormônio-peptídeos em mamíferos, isto é, utilizam o processamento de uma poliproteina para gerarem peptídeos de ação sinérgica. / Our laboratory has shown that one gene codes for the protein precursor that yields the natriuretic peptide type C (CNP) after having been processed, along with a variety of proline-rich peptides, known as bradykinin-potentiating peptides or BPPs. Showing little differences, this precursor is expressed in the venom gland and the neuroendocrine region of the Bothrops jararaca brain. All processing products have in common that they act on the cardiovascular system, lowering arterial blood pressure and heart frequency. This intriguing fact led us to question whether the different peptides display similar mechanisms of action. Surprisingly, the present study showed that the answer is negative, although we cannot, at the present time, explain in full detail how each peptide acts in the complex mechanism, responsible for vascular tonus and cardiac frequency. Historically, the demonstration that the Bradykinin-Potentiating Peptides from Bothrops jararaca (Bj-BPPs) were natural inhibitors of the angiotensin converting enzyme (ACE) had a wide medical impact. In fact, this inhibition seemed to fully explain the strong anti-hypertensive action of these peptides, therefore being employed as structural models for the development of a site-directed inhibitor, Captopril, a drug used worldwide for the treatment of systemic human arterial hypertension. Recent experimental evidences, however, suggest that the anti-hypertensive activity of the Bj-BPPs is not due exclusively to the inhibition of the ACE. Our group demonstrated that the antihypertensive action of Bj-BPP-10c, for instance, is due to the activation of L-arginine generation, which is essential for NO production, a potent vasodilator. Moreover, it also regulates the arterial baroreflex and intracellular calcium signaling, which contribute to NO production in endothelial and neuronal cells. In the present work we studied the mechanism of action of other Bj-BPPs found in the above mentioned precursor. We showed that the mechanism of action of Bj-BPP-5a involves bradykinin B2 receptor, the muscarinic receptor, subtype M1, and NO production. Bj-BPP-11e probably acts on a membrane receptor, thereby explaining its effects on cardiovascular parameters. The mechanism of action of Bj-BPP-12b might be explained by Bk potentiation and/or by ACE inhibition and Bj- BPP-13a action on by muscarinic receptor subtype M3 and the ASS. Interestingly, Bj-BPP-9a, which was the model molecule for the synthesis of Captopril, seems to act predominantly as a classic ACE inhibitor. Beside the pharmacological interest, our work also revealed, for the first time, that snake toxins also employ the well-known strategy in hormone-peptide generation, that is, they use the processing of a polyprotein to generate peptides which display a synergistic action. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2015-07-22T20:50:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-21 / Diversos autores sugerem que a sensibilização comportamental, caracterizada pelo aumento da atividade psicomotora em resposta à administração repetida de drogas psicoativas, parece desempenhar um papel fundamental no desenvolvimento de abuso e dependência, aumentando a propriedade reforçadora destas substâncias. Animais que desenvolvem sensibilização ao etanol apresentam diferenças na densidade de receptores de alguns neurotransmissores e também na resposta à administração de agonistas e antagonistas destes receptores. A sensibilização comportamental é um fenômeno complexo que envolve diferentes fatores, sendo afetada pelo ambiente, possuindo um componente de aprendizagem. Para avaliar a influência da capacidade de aprendizagem no processo de sensibilização ao efeito estimulante do etanol, no presente estudo comparamos o desempenho de dois grupos de animais com diferentes níveis de sensibilização (alta e baixa) em dois tipos de tarefas (apetitiva e aversiva). Também avaliamos a influência de uma droga amnésica (escopolamina) no desenvolvimento e expressão da sensibilização. Foi observado que animais com diferentes níveis de sensibilização não diferiram quanto à capacidade de aprendizagem após o tratamento crônico com etanol, independentemente do tipo de tarefa. A escopolamina quando administrada no hipocampo dorsal simultaneamente ao tratamento crônico com etanol não alterou o desenvolvimento da sensibilização. Porém, quando administrada por via subcutânea, provocou aumento mais acentuado nos níveis de atividade locomotora em animais que já haviam desenvolvido alta sensibilização do que nos animais que haviam desenvolvido baixa sensibilização ou no grupo controle. Este fenômeno não foi observado quando a administração de escopolamina foi realizada diretamente no núcleo accumbens, e quando administrada em combinação com etanol, foi capaz de bloquear a sensibilização. Estes dados sugerem que o sistema colinérgico atue como um neuromodulador do processo de sensibilização. Porém, parece agir de maneira diferente dependendo do nível de sensibilização desenvolvido pelo animal. / Several authors suggest that behavioral sensitization, characterized as psychomotor activity increase in response to psychoactive drugs repeated administration, seems to play a fundamental role in the development of abuse and dependence, increasing the reinforcement property of these substances. Animals that develop sensitization to ethanol differ regarding the binding to some neurotransmitter receptors and also differ regarding the response to the administration of agonists and antagonists of these receptors. Behavioral sensitization is a complex phenomenon that involves different factors, being affected by environment and learning. To evaluate the influence of learning capacity in the sensitization process, in the present study we compared the performance of two groups of mice that presented different levels of sensitization (high and low) in two different learning tasks (appetitive and aversive). We also evaluated the influence of an amnestic drug (scopolamine) in the development and expression of sensitization. It was observed that mice with different levels of sensitization did not differ regarding their learning capacity after chronic treatment with ethanol, in both tasks. Scopolamine, when administered in the dorsal hippocampus simultaneously with ethanol treatment, did not alter the sensitization development. However, when administered subcutaneously it induced higher levels of locomotor activity in those animals that had already developed high sensitization than in low sensitized mice or in the control group. This phenomenon was not observed when scopolamine was administered directly in the nucleus accumbens. When administered in combination with ethanol, it blocked the sensitization. These data suggest that the cholinergic system acts as a neuromodulator in the sensitization process. However, the cholinergic system seems to act in different ways depending on the level of sensitization developed by the animal. / TEDE / BV UNIFESP: Teses e dissertações

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / The effects of the acute administration of yangambin (25, 50 and 75 mg/kg intraperitoneal and oral), were studied in some animals behavioral models (open field, rotarod, forced swimming test, barbiturate-induced sleeping time, hole board, elevated plus maze, pentilenotetrazole-induced convulsion). Binding in vitro with differents concentrations of yangambin (0.5-200 microlitre), had been carried out to evaluate its interaction with the dopaminergic receptors (D1- and D2-like), muscarinic receptors (M1+M2)-like and serotonergic receptors (5-HT2)-like, as well as, HPLC studies to determine the effects of yangambin (25, 50 e 75 mg/kg, i.p.) after 24 h of its acute administration on the monoamines levels and its metabolites in mice motor cortex and striatum. The results showed that yangambin induced a significant reduction in the locomotor activity and the frequencies of rearing and grooming in the open field test, indicative of possible ansiolytic-like effect. These results can have related with the dopaminergic system, since that it had interaction of the yangambin with D1- e D2-sÃmile receptors, in striatum and D2-sÃmile in motor cortex, followed by a dopamine reduction, indicating a probable dopaminergic antagonistic action. The yangambin did not cause alteration in the motor coordination of the animals in the rotarod test, suggesting that the reduction of the locomotor activity can involve central action. It had a significant increase in the immobility of the mice in the forced swimming test induced by the yangambin. This effect, taken together with the reduction of the dopamine, noradrenaline and serotonin induced by yangambin in striatum, can explain its depressant effect in this model. Moreover, corroborating these results, the yangambin increased pentobarbital-induced sleeping time in treated mice, suggestive of central depressant effect. Yangambin in the doses used in this work, did not protect the animals from pentilenotetrazole-induced convulsions, suggesting that this effect depends on the used dose. In the hole board test, the yangambin increased the number of the head dips, in all the doses studied, intraperitoneal or oral, demonstrating ansiolytic activity. The ansiolytic effect of yangambin (75 mg/kg, i.p. and 25, 50 and 75 mg/kg, p.o.) was also confirmed in the elevated plus maze, where it presented significant increase in the percentage of the entries number in the open arms and the percentage of the time of permanence in the open arms. Yangambin 50 and 75 mg/kg, p.o., also increased the number of entries and the time of permanence in the open arms, respectively. However, yangambin 25 and 50 mg/kg, i.p., presented ansiogenic effect evidenced by the reduction of the time of permanence in the open arms which probably due to the absence of the formation of some active metabolite generated in the first-pass metabolism. The ansiolytic effect induced for yangambin 75 mg/kg, p.o., in the plus maze, was reverted with flumazenil (2.5 mg/kg, i.p.), indicating the possible participation of the GABAergic receptors in its mechanism of action. The ansiolytic effect of the yangambin, observed in the hole board and the plus maze test, was followed by a reduction of noradrenaline and serotonin in striatum, however, in the motor cortex, yangambin (75 mg/kg, i.p.), induced an increase of the noradrenaline levels, as well as yangambin (25, 50 and 75 mg/kg, i.p.) induced serotonin increase, demonstrating that the ansiolytic effect associated to the reduction of noradrenaline and serotonin depends on the cerebral area. The blockade of the dopaminergic receptors induced by yangambin was synergic to its agonist action on the cholinergic receptors, since that it did not modify the reduction of the locomotive activity of the animals in the open field test. The present work shows an interaction between the systems dopaminergic, cholinergic, serotonergic and GABAergic, that suggest the importance of yangambin in illnesses that modify these systems of neurotransmission. The yangambin presented compatible behavioural and neurochemical alterations with ansiolytic-like effect. / Os efeitos da administraÃÃo aguda da iangambina (25, 50 e 75 mg/kg, por via intraperitoneal e oral), foram estudados em vÃrios modelos animais de comportamento (campo aberto, rota rod, nado forÃado, tempo de sono induzido por pentobarbital, placa perfurada, labirinto em cruz elevado, convulsÃo induzida por pentilenotetrazol). Binding in vitro com diferentes concentraÃÃes de iangambina (0,5-200 microlitros), foram realizados para avaliar sua interaÃÃo com os receptores dopaminÃrgicos (D1- e D2-sÃmile), receptores muscarÃnicos (M1+M2)-sÃmile e receptores serotonÃrgicos (5-HT2)-sÃmile, bem como, estudo em HPLC para determinar os efeitos da iangambina (25, 50 e 75 mg/kg,i.p.) apÃs 24 horas de sua administraÃÃo aguda sobre os nÃveis de monoaminas e seus metabÃlitos em cÃrtex motor e corpo estriado de camundongos. Os resultados mostraram que a iangambina induziu uma diminuiÃÃo significativa na atividade locomotora e nas freqÃÃncias de rearing e grooming no teste de campo aberto, indicativo de possÃvel efeito ansiolÃtico. Estes resultados podem estar relacionados com o sistema dopaminÃrgico, desde que houve interaÃÃo da iangambina com os receptores D1- e D2-sÃmile, em corpo estriado e D2-sÃmile em cÃrtex motor, acompanhado de uma reduÃÃo de dopamina, indicando uma provÃvel aÃÃo antagonista dopaminÃrgica. A iangambina nÃo causou alteraÃÃo na coordenaÃÃo motora dos animais no teste de rota rod, sugerindo que a reduÃÃo da atividade locomotora possa envolver aÃÃo central. Houve um aumento significativo na imobilidade dos camundongos no teste do nado forÃado induzido pela iangambina. Este efeito, juntamente com a reduÃÃo da dopamina, noradrenalina e serotonina induzida pela iangambina em corpo estriado, pode explicar seu efeito depressor neste modelo. AlÃm disso, corroborando estes resultados, a iangambina potenciou o tempo de sono induzido pelo pentobarbital em camundongos, sugestivo de efeito depressor central. Iangambina nas doses empregadas neste trabalho, nÃo protegeu os animais das convulsÃes induzidas por pentilenotetrazol, sugerindo que este efeito depende da dose usada. No teste da placa perfurada, a iangambina aumentou o nÃmero de head dips, em todas as doses estudadas, por via intraperitoneal ou oral, demonstrando atividade ansiolÃtica. O efeito ansiolÃtco da iangambina (75 mg/kg, i.p e 25, 50 e 75 mg/kg, v.o.) tambÃm foi confirmado no teste do labirinto em cruz elevado, onde apresentou aumento significativo na percentagem do nÃmero de entradas nos braÃos abertos e na percentagem do tempo de permanÃncia nos braÃos abertos. Iangambina (50 e 75 mg/kg, v.o.) tambÃm aumentou o nÃmero de entradas e o tempo de permanÃncia nos braÃos abertos, respectivamente. No entanto, iangambina 25 e 50 mg/kg, i.p., apresentou efeito ansiogÃnico evidenciado pela reduÃÃo do tempo de permanÃncia nos braÃos abertos o que provavelmente pode dever-se a ausÃncia da formaÃÃo de algum metabÃlito ativo gerado no metabolismo de primeira passagem. O efeito ansiolÃtico induzido pela iangambina 75 mg/kg, v.o., no modelo do labirinto, foi revertido com o flumazenil (2,5 mg/kg,i.p), indicando a possÃvel participaÃÃo dos receptores GABAÃrgicos no seu mecanismo de aÃÃo. O efeito ansiolÃtico da iangambina, observado no teste da placa perfurada e no labirinto em cruz elevado, foi acompanhado por uma reduÃÃo de noradrenalina e serotonina em corpo estriado, no entanto, em cÃrtex motor, iangambina (75 mg/kg, i.p.), induziu um aumento dos nÃveis de noradrenalina, assim como iangambina (25, 50 e 75 mg/kg, i.p.) induziu aumento de serotonina, demonstrando que o efeito ansiolitico associado a reduÃÃo de noradrenalina e serotonina depende da Ãrea cerebral. A iangambina interagiu com receptores muscarÃnicos em cÃrtex motor e corpo estriado. O bloqueio dos receptores dopaminÃrgicos induzido pela iangambina foi sinÃrgico à sua aÃÃo agonista sobre os receptores colinÃrgicos, desde que nÃo alterou a reduÃÃo da atividade locomotora dos animais no modelo de campo aberto. O presente trabalho mostra uma interaÃÃo entre os sistemas dopaminÃrgico, colinÃrgico, serotonÃrgico e GABAÃrgico, revelando a importÃncia da iangambina em doenÃas que alteram estes sistemas de neurotransmissÃo. A iangambina apresentou alteraÃÃes comportamentais e neuroquÃmicas compatÃveis com efeito ansiolÃtico-sÃmile.