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Id: lil-751361
Autor: Kiani, Farhoush; Abbaszadeh, Mehran; Pousti, Mohammad; Koohyar, Fardad.
Título: Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution
Fonte: Braz. j. pharm. sci;51(1):213-219, Jan-Mar/2015. tab, graf.
Idioma: en.
Resumo: In the present work, acid dissociation constant (pKa) values of muscimol derivatives were calculated using the Density Functional Theory (DFT) method. In this regard, free energy values of neutral, protonated and deprotonated species of muscimol were calculated in water at the B3LYP/6-31G(d) basis sets. The hydrogen bond formation of all species had been analyzed using the Tomasi's method. It was revealed that the theoretically calculated pKa values were in a good agreement with the existing experimental pKa values, which were determined from capillary electrophoresis, potentiometric titration and UV-visible spectrophotometric measurements.

No presente trabalho, calculou-se a constante de dissociação do ácido (pKa) dos derivados de muscimol, utilizando-se o método da teoria do funcional de densidade (DFT). Com esse objetivo, calcularam-se os valores das espécies neutra, protonada e desprotonada do muscimol em água em base B3LYP/6-31G(d). A formação da ligação de hidrogênio de todas as espécies foi analisada utilizando o método de Tomasi. Demonstrou-se que os valores de pKa calculados teoricamente estavam em boa concordância com os valores experimentais disponíveis, determinados por eletroforese capilar, titulação potenciométrica e medidas por espectrofotometria UV-visível.
Descritores: Dissolução
Muscimol/análise
-Ligação de Hidrogênio
Responsável: BR1.1 - BIREME


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Id: lil-556857
Autor: Nascimento, J. O. G; Zangrossi Júnior, H; Viana, M. B.
Título: Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;43(9):869-873, Sept. 2010. ilus.
Idioma: en.
Resumo: The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.
Descritores: Transtornos de Ansiedade/fisiopatologia
Agonistas de Receptores de GABA-A/farmacologia
Hipotálamo/efeitos dos fármacos
Muscimol/farmacologia
Transtorno de Pânico/etiologia
Transtorno de Pânico/fisiopatologia
-Transtornos de Ansiedade/etiologia
Reação de Fuga/efeitos dos fármacos
Hipotálamo/fisiopatologia
Aprendizagem em Labirinto/efeitos dos fármacos
Atividade Motora/efeitos dos fármacos
Ratos Wistar
Limites: Animais
Masculino
Ratos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


  3 / 12 LILACS  
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Id: lil-505427
Autor: Margatho, L. O; Elias, L. L. K; Antunes-Rodrigues, J.
Título: GABA in the central amygdaloid nucleus modulates the electrolyte excretion and hormonal responses to blood volume expansion in rats
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;42(1):114-121, Jan. 2009. ilus.
Idioma: en.
Conferência: Apresentado em: Miguel R. Covian Symposium, 4, Ribeirão Preto, May 23-25, 2008.
Projeto: FAPESP; . CNPq.
Resumo: We investigated the involvement of GABAergic mechanisms of the central amygdaloid nucleus (CeA) in unanesthetized rats subjected to acute isotonic or hypertonic blood volume expansion (BVE). Male Wistar rats bearing cannulas unilaterally implanted in the CeA were treated with vehicle, muscimol (0.2 nmol/0.2 µL) or bicuculline (1.6 nmol/0.2 µL) in the CeA, followed by isotonic or hypertonic BVE (0.15 or 0.3 M NaCl, 2 mL/100 g body weight over 1 min). The vehicle-treated group showed an increase in sodium excretion, urinary volume, plasma oxytocin (OT), and atrial natriuretic peptide (ANP) levels compared to control rats. Muscimol reduced the effects of BVE on sodium excretion (isotonic: 2.4 ± 0.3 vs vehicle: 4.8 ± 0.2 and hypertonic: 4.0 ± 0.7 vs vehicle: 8.7 ± 0.6 µEq·100 g-1·40 min-1); urinary volume after hypertonic BVE (83.8 ± 10 vs vehicle: 255.6 ± 16.5 µL·100 g-1·40 min-1); plasma OT levels (isotonic: 15.3 ± 0.6 vs vehicle: 19.3 ± 1 and hypertonic: 26.5 ± 2.6 vs vehicle: 48 ± 3 pg/mL), and ANP levels (isotonic: 97 ± 12.8 vs vehicle: 258.3 ± 28.1 and hypertonic: 160 ± 14.6 vs vehicle: 318 ± 16.3 pg/mL). Bicuculline reduced the effects of isotonic or hypertonic BVE on urinary volume and ANP levels compared to vehicle-treated rats. However, bicuculline enhanced the effects of hypertonic BVE on plasma OT levels. These data suggest that CeA GABAergic mechanisms are involved in the control of ANP and OT secretion, as well as in sodium and water excretion in response to isotonic or hypertonic blood volume expansion.
Descritores: Tonsila do Cerebelo/efeitos dos fármacos
Bicuculina/farmacologia
Volume Sanguíneo/efeitos dos fármacos
Agonistas GABAérgicos/farmacologia
Antagonistas GABAérgicos/farmacologia
Muscimol/farmacologia
-Tonsila do Cerebelo/fisiologia
Fator Natriurético Atrial/sangue
Bicuculina/administração & dosagem
Volume Sanguíneo/fisiologia
Diurese/efeitos dos fármacos
Diurese/fisiologia
Agonistas GABAérgicos/administração & dosagem
Antagonistas GABAérgicos/administração & dosagem
Muscimol/administração & dosagem
Ocitocina/sangue
Ratos Wistar
Sódio/urina
Limites: Animais
Masculino
Ratos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


  4 / 12 LILACS  
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Id: lil-435718
Autor: Almeida, Rosa M. M de; Giovenardi, Márcia; Damra, Adriana; Frey, Rosana M; Rasia-Filho, Alberto A.
Título: Plus-maze following the microinjection of muscimol into the dorsal periaqueductal gray of the rat / Performance no labirinto em cruz elevado após microinjeção de muscimol na substância cinzenta periaquedutal dorsal do rato
Fonte: Rev. bras. psiquiatr;28(1):80-82, mar. 2006. ilus, tab.
Idioma: en; pt.
Descritores: GABAérgicos/farmacologia
Aprendizagem em Labirinto/efeitos dos fármacos
Muscimol/farmacologia
Substância Cinzenta Periaquedutal/efeitos dos fármacos
-Ansiolíticos/farmacologia
Microinjeções
Ratos Wistar
Limites: Animais
Masculino
Ratos
Tipo de Publ: Carta
Responsável: BR1.1 - BIREME


  5 / 12 LILACS  
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Id: lil-431562
Autor: Duarte, T. T; Corrêa, S. A. L; Santana, U. J; Pereira, A. S. F; Hoffmann, A.
Título: Agonistic-like responses from the torus semicircularis dorsalis elicited by GABA A blockade in the weakly electric fish Gymnotus carapo
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;39(7):945-955, July 2006. ilus.
Idioma: en.
Projeto: Fundação de Amparo à Pesquisa do Estado de São Paulo.
Resumo: Findings by our group have shown that the dorsolateral telencephalon of Gymnotus carapo sends efferents to the mesencephalic torus semicircularis dorsalis (TSd) and that presumably this connection is involved in the changes in electric organ discharge (EOD) and in skeletomotor responses observed following microinjections of GABA A antagonist bicuculline into this telencephalic region. Other studies have implicated the TSd or its mammalian homologue, the inferior colliculus, in defensive responses. In the present study, we explore the possible involvement of the TSd and of the GABA-ergic system in the modulation of the electric and skeletomotor displays. For this purpose, different doses of bicuculline (0.98, 0.49, 0.245, and 0.015 mM) and muscimol (15.35 mM) were microinjected (0.1 æL) in the TSd of the awake G. carapo. Microinjection of bicuculline induced dose-dependent interruptions of EOD and increased skeletomotor activity resembling defense displays. The effects of the two highest doses showed maximum values at 5 min (4.3 ± 2.7 and 3.8 ± 2.0 Hz, P < 0.05) and persisted until 10 min (11 ± 5.7 and 8.7 ± 5.2 Hz, P < 0.05). Microinjections of muscimol were ineffective. During the interruptions of EOD, the novelty response (increased frequency in response to sensory novelties) induced by an electric stimulus delivered by a pair of electrodes placed in the water of the experimental cuvette was reduced or abolished. These data suggest that the GABA-ergic mechanisms of the TSd inhibit the neural substrate of the defense reaction at this midbrain level.
Descritores: Comportamento Animal/fisiologia
Bicuculina/farmacologia
Gimnotiformes/fisiologia
Mesencéfalo/fisiologia
Muscimol/farmacologia
-Comportamento Animal/efeitos dos fármacos
Bicuculina/administração & dosagem
Mecanismos de Defesa
Interações Medicamentosas/fisiologia
Estimulação Elétrica
Órgão Elétrico/efeitos dos fármacos
Órgão Elétrico/fisiologia
Agonistas GABAérgicos/farmacologia
Antagonistas GABAérgicos/farmacologia
Microinjeções
Mesencéfalo/efeitos dos fármacos
Movimento/efeitos dos fármacos
Movimento/fisiologia
Muscimol/administração & dosagem
Vias Neurais/efeitos dos fármacos
Vias Neurais/fisiologia
Limites: Animais
Responsável: BR1.1 - BIREME


  6 / 12 LILACS  
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Id: lil-414724
Autor: Bueno, C. H; Zangrossi Júnior, H; Viana, M. B.
Título: The inactivation of the basolateral nucleus of the rat amygdala has an anxiolytic effect in the elevated T-maze and light/dark transition tests
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;38(11):1697-1701, Nov. 2005. ilus.
Idioma: en.
Resumo: Pharmacological evidence indicates that the basolateral nucleus of the amygdala (BLA) is involved in the mediation of inhibitory avoidance but not of escape behavior in the elevated T-maze test. These defensive responses have been associated with generalized anxiety disorder (GAD) and panic disorder, respectively. In the present study, we determined whether the BLA plays a differential role in the control of inhibitory avoidance and escape responses in the elevated T-maze. Male Wistar rats (250-280 g, N = 9-10 in each treatment group) were pre-exposed to one of the open arms of the maze for 30 min and 24 h later tested in the model after inactivation of the BLA by a local injection of the GABA A receptor agonist muscimol (8 nmol in 0.2 æL). It has been shown that a prior forced exposure to one of the open arms of the maze, by shortening latencies to withdrawal from the open arm during the test, improves the escape task as a behavioral index of panic. The effects of muscimol in the elevated T-maze were compared to those caused by this GABA agonist in the avoidance reaction generated in the light/dark transition test. This defensive behavior has also been associated with GAD. In the elevated T-maze, intra-BLA injection of muscimol impaired inhibitory avoidance (control: 187.70 ± 14.90 s, muscimol: 37.10 ± 2.63 s), indicating an anxiolytic effect, without interfering with escape performance. The drug also showed an anxiolytic effect in the light/dark transition test as indicated by the increase in the time spent in the lighted compartment (control: 23.50 ± 2.45 s, muscimol: 47.30 ± 4.48 s). The present findings point to involvement of the BLA in the modulation of defensive responses that have been associated with GAD.
Descritores: Transtornos de Ansiedade
Agonistas GABAérgicos/farmacologia
Tonsila do Cerebelo/efeitos dos fármacos
Aprendizagem da Esquiva/fisiologia
Muscimol/farmacologia
Reação de Fuga/fisiologia
-Transtornos de Ansiedade
Agonistas GABAérgicos/administração & dosagem
Tonsila do Cerebelo/fisiologia
Aprendizagem da Esquiva/efeitos dos fármacos
Escuridão
Luz
Aprendizagem em Labirinto
Microinjeções
Muscimol/administração & dosagem
Ratos Wistar
Reação de Fuga/efeitos dos fármacos
Limites: Animais
Masculino
Ratos
Responsável: BR1.1 - BIREME


  7 / 12 LILACS  
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Colombari, E
Menani, J. V
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Id: lil-403868
Autor: Callera, J. C; Colombari, E; De Luca Júnior, L. A; Menani, J. V.
Título: The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;38(7), July 2005. ilus.
Idioma: en.
Projeto: FAPESP.
Resumo: We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 æg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections.
Descritores: Pressão Sanguínea/efeitos dos fármacos
Agonistas GABAérgicos/farmacologia
Frequência Cardíaca/efeitos dos fármacos
Receptores de GABA-A/efeitos dos fármacos
Serotonina/farmacologia
Núcleo Solitário/efeitos dos fármacos
-Baclofeno/farmacologia
Bradicardia/fisiopatologia
Hipotensão/fisiopatologia
Muscimol/farmacologia
Ratos Sprague-Dawley
Receptores de GABA-A/fisiologia
Serotonina/administração & dosagem
Núcleo Solitário/fisiologia
Limites: Animais
Masculino
Ratos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


  8 / 12 LILACS  
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Id: lil-292235
Autor: López Alonso, Verónica Elsa; Mancilla Díaz, Juan Manuel; Durán Diaz, Angel; Escartín Pérez, Erick Rodrigo; Cobos Zapiain, Guillermo; Garfías Arvizu, Alfonso.
Título: Efectos de la administración central de agonistas GABAérgicos sobre la microestructura de la conducta alimenticia. Estudio experimental en ratas / Response to central administration of GABAergic agents on the microestructure of feeding behaviour. Experimental trial in rats
Fonte: Rev. sanid. mil;54(6):279-84, nov.-dic. 2000. tab.
Idioma: es.
Resumo: Debido a la administración de muscimol en el HVM (hipotálamo ventromedial) la ingesta de carbohidratos y la ingesta total se incrementaron; conductualmente este aumento de la ingesta de alimento se caracterizó por el aumento del tiempo total, asociado a un incremento en la duración de los episodios alimentarios. La administración de baclofén en el HVM incrementó la ingesta de carbohidratos y la ingesta total, este aumento se caracterizó por episodios alimentarios menos frecuentes pero más largos. Se confirma que la estimulación de los receptores GABAA y GABAB en el HVM inducen la alimentación y se concluye que el sistema GABAérgico está involucrado en el control de la conducta alimenticia.
Descritores: Comportamento Alimentar/efeitos dos fármacos
Agonistas GABAérgicos/administração & dosagem
Muscimol/administração & dosagem
Núcleo Caudado
-Carboidratos da Dieta
Putamen/efeitos dos fármacos
Limites: Animais
Ratos
Responsável: MX1.1 - CENIDSP - Centro de Información para Decisiones en Salud Pública


  9 / 12 LILACS  
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Id: lil-196346
Autor: Dias, Elisa C; Segraves, Mark A.
Título: The primate frontal eye field and the generation of saccadic eye movements: comparison of lesion and acute inactivation/activation studies
Fonte: Rev. bras. biol;56(supl.1,pt.2):239-55, dez. 1996. ilus.
Idioma: en.
Conferência: Apresentado em: International Symposium of Neuroscience, Belém, 1996.
Projeto: National Institute of Health.
Resumo: The frontal eye field (FEF) of monkeys has been repeatedly implicated in the generation of saccadic eye movements by various experimental approaches. Electrical stimulation of most of the FEF produces saccadic eye movements, many cells have activities related to saccades, and it has anatomical connections with many other oculomotor ares. Surprisingly, complete lesions of the FEF have remarkably little effect on oculomotor behavior. Only when more cognitive aspects are tested is a deficit clearly detected. In contrast, acute inactivation of the FEF on monkeys with the GABA agonist muscimol produced much more severe oculomotor impairment. This difference is probably due to the acute nature of the muscimol effect, which does not allow time for reorganization of the control of eye movements before testing begins. In addition, acute activation of the FEF with the GABA antagonist bicuculline caused the monkey to make irrepressible saccades of the same dimensions as those electrically elicited at the site. These experiments further confirm the strong involvement of the FEF in the control of saccadic eye movements and fixation.
Descritores: Bicuculina/farmacologia
Olho/fisiologia
Agonistas GABAérgicos/farmacologia
Antagonistas GABAérgicos/farmacologia
Macaca/fisiologia
Muscimol/farmacologia
Movimentos Sacádicos/fisiologia
Limites: Animais
Feminino
Tipo de Publ: Research Support, U.S. Gov't, P.H.S.
Responsável: BR1.1 - BIREME


  10 / 12 LILACS  
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Quevedo, J
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Id: lil-188432
Autor: Zanatta, M. S; Quillfeldt, J. H; Schaeffer, E; Schmitz, P. K; Quevedo, J; Medina, J. H; Izquierdo, I.
Título: Involviment of the hippocampus, amygdala, entorhinal cortex and posterior parietal cortex in memory consolidation
Fonte: Braz. j. med. biol. res = Rev. bras. pesqui. méd. biol;30(2):235-40, Feb. 1997. ilus, graf.
Idioma: en.
Resumo: A total of 182 young adult male Wistar rats were bilaterally implanted with cannulae into the CA1 region of the dorsal hippocampus and into the amygdaloid nucleus, the entorhinal cortex, and the posterior parietal cortex. After recovery, the animals were trained in a stepdown inhibitory avoidance task. At various times after training (0, 30, 60 or 90 min) the animals received a 0.5-mul microinfusion of vehicle (saline) or O.5 mug of muscimol dissolved in the vehicle. A retention test was carried out 24 h after training. Retention test performance was hindered by muscimol administered into both the hippocampus and amygdala at 0 but not at 30 min posttraining. The drug was amnestic when given into the entorhinal cortex 30, 60 or 90 min after training, or into the parietal cortex 60 or 90 min after training, but not before. These findings suggest a sequential entry in operation, during the posttraining period, of the hippocampus and amygdala, the entorhinal cortex, and the posterior parietal cortex in memory processing.
Descritores: Tonsila do Cerebelo/fisiologia
Córtex Entorrinal/fisiologia
Hipocampo/fisiologia
Memória/fisiologia
Muscimol/farmacologia
Lobo Parietal/fisiologia
-Tonsila do Cerebelo/efeitos dos fármacos
Córtex Entorrinal/efeitos dos fármacos
Hipocampo/efeitos dos fármacos
Lobo Parietal/efeitos dos fármacos
Ratos Wistar
Limites: Ratos
Masculino
Animais
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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