Repositório Institucional - Unifesp :: Navegando por Palavras-chave "GABA"

Navegando por Palavras-chave "GABA"

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Acesso aberto (Open Access)
Análise dos efeitos do extrato padronizado de Ginkgo biloba L. na aquisição e na extinção do medo condicionado
(Universidade Federal de São Paulo, 2013-04-25) Zamberlam, Claudia Raquel [UNIFESP]; Cerutti, Suzete Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Dados anteriores no nosso laboratório mostraram que os tratamentos a curto ou a longo prazo com o extrato padronizado de Ginkgo biloba L. (EGb) modulam a aquisição da Resposta Emocional Condicionda (REC). Essas modificações estavam associadas ao aumento da expressão gênica e proteica de CREB-1 e GFAP e redução de GAP-43 no hipocampo de ratos e, em paralelo, às modificações observadas no córtex pré-frontal e complexo amigdaloide. A compreensão dos mecanismos celulares e moleculares subjacentes a estes processos poderá no ajudar a compreender os efeitos do EGb no sistema nervoso central. Diversos estudos têm sugerido que os sistemas de neurotransmissão glutamatérgico, gabaérgico e serotoninérgico são alvos estratégicos importantes por participar da formação de memória do medo condicionado. Para compreender a participação dos diferentes sistemas nas etapas da formação da memória do medo condicionado, os animais foram distribuídos aleatoriamente em 4 grupos de acordo com o momento de administração das substâncias, a fim de se avaliar a aquisição (Grupo 1) e evocação do medo condicionado (Grupo 2) ou da aquisição (Grupo 3) e evocação da extinção (Grupo 4), através do teste da REC. O grupo 1 (1A-D, n=20/grupo) recebeu as drogas antes da aquisição da REC (Treino 1, Tr1), sendo que metade (n=10/grupo) dos animais foram eutanasiados após o Teste 1 (T1) e os demais após o Teste 2 (T2); no grupo 2 (n=10/grupo) a droga foi administrada antes do Teste1 (T1) e os animais foram eutanasiados 3 ou 24 hs após o término do T1; o grupo 3 (n=10/grupo) recebeu as drogas antes do Treino da extinção (Treino 2, Tr2) e foi eutanasiado 3 ou 24 hs após, e no grupo 4 (n=10/grupo) as drogas foram administradas antes do T2 e os animais foram eutanasiados 3 ou 24 hs após. Os tratamentos com uma única dose do EGb (250 mg.Kg-1, 500 mg.Kg-1 ou 1000 mg.Kg-1), antagonistas específicos para receptores glutamatérgicos do tipo NMDA-NR2B (RO 256981, 10 mg.Kg-1), do tipo GABAA (Picrotoxina, 0,75 mg.Kg-1) e serotoninérgicos do tipo 5-HT1A (SWAY 100135, 0,3 mg.Kg-1) ou agonistas (NMDA, Diazepam e Buspirona) e as soluções veículos (Tween ou salina) foram administradas 30 ou 20 min antes da sessão experimental, respectivamente. Ratos tratados com antagonistas + EGb receberam as drogas 50 min antes da sessão. A análise da Taxa de Supressão (TS) da resposta de lamber mostra que ratos tratados com EGb na dose de 250 mg.Kg-1 antes do Tr1 e na dose de 1000 mg.Kg-1 antes do Tr2 tiveram maior supressão da resposta de lamber, comparados aos grupos controle positivo (Diazepam 10 mg.Kg-1) e negativo (Tween 80-12%) (P<0,05), favorecendo a aquisição da extinção da memória do medo condicionado. Dados obtidos com a administração dos antagonistas sugerem que o EGb modula a aquisição do medo condicionado através dos receptores NR2B e 5-HT1A nas doses de 250 mg.K-1 e 500 mg.Kg-1 e reduz a supressão na dose de 1000 mg.Kg-1 via receptor GABAA. Ainda, na maior dose o EGb favorece a recuperação espontânea do medo condicionado quando administrado antes do treino e antes do teste da extinção. Em conjunto os dados evidenciam os efeitos do EGb na formação da memória do medo condicionado e os mecanismos neuroquímicos envolvidos em cada etapa.
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Anticonvulsant and GABA uptake inhibition properties of venom fractions from the spiders Parawixia bistriata and Scaptocosa raptoria
(Swets Zeitlinger Publishers, 2002-09-01) Rodrigues, Marcelo Cairrão Araujo; Ribeiro, Alessandra Mussi; Pizzo, Andrea Baldocchi; Fontana, Andreia Cristina Karklin; Beleboni, Renê de Oliveira; Coutinho-Netto, Joaquim; Miranda, Antonio de [UNIFESP]; Santos, Wagner Ferreira dos; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
In this article we describe an in vivo anticonvulsant effect from denatured crude venom and partially isolated fractions from two spiders: Parawixia bistriata and Scaptocosa raptoria. Intracerebroventricular injections of these venoms and fractions abolished rat convulsive tonic-clonic seizures induced by picrotoxin, bicuculline and pentylenetetrazole, and also, inhibited GABA uptake in synaptosomes of rat cerebral cortex. the venoms described in this work seems to be promising tools for the study of the GABAergic system, and may be a potential source for new anticonvulsant drugs.
Acesso aberto (Open Access)
Cardiovascular responses to microinjections of GABA or anesthetics into the rostral ventrolateral medulla of conscious and anesthetized rats
(Associação Brasileira de Divulgação Científica, 2003-09-01) Lacerda, J.e.c. [UNIFESP]; Campos, Ruy Ribeiro [UNIFESP]; Araujo, G.c. [UNIFESP]; Andreatta-van Leyen, S. [UNIFESP]; Lopes, Oswaldo Ubriaco [UNIFESP]; Guertzenstein, P.g. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 ± 3.6 to 110 ± 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 ± 8.9 to 76 ± 8.8 mmHg, N = 7) or pentobarbital (from 118 ± 4.5 to 57 ± 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 ± 4.1 to 92 ± 5.9 mmHg, N = 7) and anesthetized rats (from 123 ± 6.9 to 87 ± 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.
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Cerebrospinal fluid GABA levels in chronic migraine with and without depression
(Elsevier B.V., 2006-05-23) Vieira, DSS; Naffah-Mazacoratti, M. G.; Zukerman, E.; Soares, CAS; Alonso, E. O.; Faulhaber, MHW; Cavalheiro, E. A.; Peres, MFP; Universidade Federal de São Paulo (UNIFESP)
Psychiatric comorbidity is one of the key elements in chronic migraine (CM) management. Depression is particularly common in these patients, occurring in up to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA) levels may be decreased in animal models of depression. Also, clinical studies have reported low level in mood disorder patients for both plasma and cerebrospinal fluid (CSF) GABA. We hypothesized that low GABA levels in the brain might be related to the depression associated with CM. We studied 14 chronic migraine patients, with or without depression, compared to age-and sex-matched controls. CSF GABA levels were measured by HPLC. CSF GABA levels showed significant lower levels in depressed patients than those without depression. No difference was found when comparing patients versus controls. A GABA deficiency may be the underlying mechanism of depression in CM. Hence, preventive therapies modulating GABA neurotransmission could be used in CM associated with depression. (c) 2006 Elsevier B.V. All rights reserved.
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Changes in GABAergic inputs in the paraventricular nucleus maintain sympathetic vasomotor tone in chronic heart failure
(Elsevier B.V., 2012-11-02) Carillo, Bruno de Arruda [UNIFESP]; Oliveira-Sales, Elizabeth Barbosa de [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Tufik, Sergio [UNIFESP]; Hipólide, Débora Cristina [UNIFESP]; Santos, A. A. [UNIFESP]; Tucci, Paulo José Ferreira [UNIFESP]; Bergamaschi, Cassia Toledo [UNIFESP]; Campos, Ruy Ribeiro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The paraventricular nucleus (PVN) of the hypothalamus is an important region of the brain involved in the regulation of sympathetic vasomotor tone. Accumulating evidence supports the idea that a change in hypothalamic gamma-aminobutyric acid (GABA)-ergic inhibitory and glutamatergic excitatory inputs contribute to the exacerbated sympathetic drive in chronic heart failure (HF). the purpose of this study was to determine whether a possible imbalance between glutamatergic and GABAergic inputs to the PVN contributes to increased sympathetic outflow in HF in two different sympathetic territories. Renal (RSNA) and splanchnic sympathetic nerve activity (SSNA), mean arterial blood pressure (MAP) and heart rate were recorded from urethane-anesthetized HF or sham rats. the NMDA-glutamate and GABA-A receptor densities within the PVN were quantified in HF and sham rats by autoradiography. Bilateral microinjection of kynurenic acid (4 nmol) into the PVN decreased MAP and RSNA and SSNA in HF but not in sham rats. Furthermore, in response to GABA-A blockade in the PVN by bicuculline (400 pmol), hypertension and SSNA were reduced in HF compared to sham. the quantification of ionotropic NMDA receptors and GABA-A receptors in the PVN showed a significant reduction of GABA-A in HF rats; however, the NMDA density in the PVN did not differ between groups. Thus, this study provides evidence that the sympathoexcitation is maintained by an imbalance between GABAergic and glutamatergic inputs in the PVN in HF. the reduced GABAergic input results in relatively augmented glutamatergic actions in the PVN of HF rats. (C) 2012 Elsevier B.V. All rights reserved.
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DECREASED SUSCEPTIBILITY TO SEIZURES INDUCED BY BICUCULLINE AFTER TRANSIENT BILATERAL CLAMPING of the CAROTID ARTERIES in RATS
(Springer, 1991-01-01) Sieklucka, M.; Bortolotto, Z.; Heim, C.; Block, F.; Sontag, K. H.; UNIV GOTTINGEN; MAX PLANCK INST EXPTL MED; INST CLIN PATHOL; Universidade Federal de São Paulo (UNIFESP)
Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. 14 days later the animals were subjected to subcutaneous injection of (+)-bicuculline (3 or 4 mg/kg). A significantly decreased susceptibility to bicuculline-induced seizures could be observed in BCCA treated rats compared with sham operated controls. It is suggested that BCCA treatment protects animals against status epilepticus and lethal toxicity produced by bicuculline. Electrographic recordings of the BCCA animals revealed no ictal activity within 1 h after bicuculline injection. An analysis of the GABA content showed a significant increase in the hippocampus (HPC), frontal cortex (FCX), parietal cortex and substantia nigra in BCCA animals compared with controls. It is therefore possible that an increase in GABA content postsynaptically counteracts the GABA(A) antagonistic effect of bicuculline in BCCA animals thus preventing the normal seizure inducing effect of this substance.
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Effects of baclofen on reserpine-induced vacuous chewing movements in mice
(Elsevier B.V., 2006-02-15) Castro, JPMV; Frussa-Filho, R.; Fukushiro, D. F.; Silva, R. H.; Medrano, W. A.; Ribeiro, R. D.; Abilio, V. C.; Universidade Federal de São Paulo (UNIFESP)
We have described that GABA mimetic drugs present the ability to inhibit the expression of reserpine-induced oral movements. in this respect, oral movements is associated with important neuropathologies. This study investigates the effects of an acute or a repeated treatment of different doses of the GABA(B) agonist baclofen, as well as withdrawal from these treatments, on the development and/or expression of reserpine-induced vacuous chewing movements (VCM). Male mice received two injections of vehicle or of 1 mg/kg reserpine separated by 48h. in the first experiment, 24 h later, animals were acutely treated with vehicle or baclofen (1, 2 or 4 mg/kg). in the second experiment, animals were treated with vehicle or baclofen (1 or 4 mg/kg) for four consecutive days receiving a concomitant injection of 1 mg/kg reserpine (or vehicle) on Days 2 and 4. Twenty-four hours later, animals received vehicle or baclofen. Thirty minutes after the last injection, they were observed for quantification of VCM and open-field general activity. the acute administration of all the doses of baclofen abolished the manifestation of reserpine-induced VCM. Repeated treatment with 1 mg/kg baclofen induced tolerance to the ability of an acute injection of this dose to reduce VCM. Treatment with baclofen (4 mg/kg) did not modify spontaneous VCM. Acute administration of the highest dose induced a decrease in general motor activity and a potentiation of the reserpine-induced decrease in general activity. These results reinforce the involvement of GABAcrgic hypofunction in the expression of oral movements and suggest that a repeated treatment with baclofen induces compensatory changes in GABAergic transmission that can attenuate its acute property to decrease VCM. (c) 2005 Elsevier Inc. All rights reserved.
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EFFECTS of BILATERAL CLAMPING of CAROTID ARTERIES ON HIPPOCAMPAL KINDLING in RATS
(Elsevier B.V., 1991-04-01) Bortolotto, Z. A.; Heim, C.; Sieklucka, M.; Block, F.; Sontag, K. H.; Cavalheiro, E. A.; Universidade Federal de São Paulo (UNIFESP); MAX PLANCK INST EXPTL MED; UNIV GOTTINGEN; INST CLIN PATHOL
Moderate reduction of cerebral blood flow by bilateral clamping of carotid arteries (BCCA) in pentobarbital anaesthetized Wistar rats induces decreased PO2 and temperature values in vulnerable brain structures such as hippocampus and frontal cortex during the acute phase of clamping. Up to two weeks chronic increased GABA contents in hippocampus, substantia nigra and frontal cortex could be observed. During this time the development of hippocampal kindling was difficult. These results demonstrated an acute and chronic influence of GABA on most vulnerable brain structures which, however, do not lead to ischemic impacts as histological analyses demonstrate.
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Effects of gabaergic drugs on reserpine-induced oral dyskinesia
(Elsevier B.V., 2005-05-07) Peixoto, M. R.; Araujo, N. P.; Silva, R. H.; Castro, JPMV; Fukushiro, D. F.; Faria, R. R.; Zanier-Gomes, P. H.; Medrano, W. A.; Frussa-Filho, R.; Abilio, V. C.; Universidade Federal de São Paulo (UNIFESP)
Recently we have described the antidyskinetic property of the GABA mimetic drugs valproic acid and topiramate on reserpine-induced oral dyskinesia. in this respect, oral dyskinesia has been associated with important neuropathologies. the present study investigates the effects of different doses of the GABA(A) agonist tetrahydroisoxazolopyridine (THIP), of the GABA(B) agonist baclofen as well as of the GABAA modulator diazepam on the manifestation of reserpine-induced orofacial dyskinesia. Male Wistar rats received two injections of vehicle or of 1 mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with vehicle or THIP (2, 4 or 8 mg/kg), baclofen (1, 2 or 4 mg/kg) or diazepam (1, 2 or 4 mg/kg) and were observed for quantification of oral dyskinesia and open-field general activity. in order to verify the effects of these drugs per se on spontaneous oral movements, male Wistar rats were acutely treated with vehicle, 8 mg/kg THIP, 4 mg/kg baclofen or 4 mg/kg diazepam and observed for quantification of oral dyskinesia. the two highest doses of THIP or of baclofen abolished the manifestation of reserpine-induced oral dyskinesia while the lowest dose of baclofen attenuated it. Diazepam did not modify reserpine-induced oral dyskinesia at any dose tested. the highest doses of these drugs did not modify spontaneous oral movements. Reserpineinduced decrease in open-field general activity was not modified by any of the doses of THIP and diazepam or by the two lowest doses of baclofen. the highest dose of baclofen potentiated the increase in the duration of immobility induced by reserpine. These results reinforce the involvement of GABAergic hypofunction in the expression of oral dyskinesias, and support the potential therapeutic use of THIP and baclofen in the treatment of oral dyskinesias. © 2004 Elsevier B.V. All rights reserved.
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Effects of topiramate on oral dyskinesia induced by reserpine
(Elsevier B.V., 2004-12-15) Araujo, N. P.; Abilio, V. C.; Silva, R. H.; Pereira, R. C.; Carvalho, R. C.; Gonzalez, C.; Bellot, R. G.; Castro, JPMV; Fukushiro, D. F.; Rodrigues, MSD; Chinen, C. C.; Frussa, R.; Universidade Federal de São Paulo (UNIFESP)
Recently, we have described the antidyskinetic property of the GABA mimetic drug valproic acid on reserpine-induced oral dyskinesia, an animal model that has been related to tardive as well as acute dyskinesias, which are associated with important neuropathologies. the present study investigates the effects of different doses of the GABA mimetic anticonvulsant topiramate on the manifestation of reserpine-induced orofacial dyskinesia. Female EPM-M1 mice received two injections of control solution or of 0.5 mg/kg reserpine separated by 48 h. Twenty-four hours after the second reserpine or control solution injection, animals were acutely treated with control solution or topiramate (1, 3, 10 or 30 mg/kg) and were observed for quantification of oral dyskinesia or general activity in an open-field. in order to verify the effects of topiramate per se on oral dyskinesia or general activity, female EPM-M1 mice were acutely treated with control solution or 1, 3, 10 or 30 mg/kg topiramate and observed for quantification of oral dyskinesia and general activity. the highest dose of topiramate completely abolished the manifestation of reserpine-induced oral dyskinesia whereas the doses of 3 and 10 mg/kg significantly attenuated it. None of the doses of the anticonvulsant modified spontaneous locomotion frequency or oral movements, whereas spontaneous rearing frequency was decreased by 3, 10 and 30 mg/kg topiramate. the highest dose of topiramate did not modify general activity in reserpine-treated mice. These results support the potential therapeutic use of topiramate in the treatment of oral dyskinesias. (C) 2004 Elsevier Inc. All rights reserved.
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Effects of valproic acid on an animal model of tardive dyskinesia
(Elsevier B.V., 2003-06-16) Peixoto, M. F.; Abilio, V. C.; Silva, R. H.; Frussa, R.; Universidade Federal de São Paulo (UNIFESP)
GABAergic hypofunction in the basal ganglia is stated as an important mechanism underlying the pathophysiology of tardive dyskinesia. the present study investigates the effects of the GABA-mimetic drug valproic acid (VA) on the manifestation of reserpine-induced orofacial movements, an animal model of tardive dyskinesia. Male Wistar rats received two injections of control solution or of 1 mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with 50, 100, or 200 mg/kg VA or control solution and were observed for quantification of orofacial movements and of open-field general activity. the highest dose of VA inhibited the manifestation of reserpine-induced orofacial movements but none of the VA doses modified reserpine-induced decrease in open-field general activity. These results support the potential of VA as an effective pharmacological tool in the treatment of tardive dyskinesia. (C) 2003 Elsevier Science B.V. All rights reserved.
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Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats
(Amer Physiological Soc, 2010-07-01) Ogihara, Cristiana A. [UNIFESP]; Schoorlemmer, Gerhardus H. M. [UNIFESP]; Levada, Adriana C.; Pithon-Curi, Tania C.; Curi, Rui; Lopes, Oswaldo Ubriaco [UNIFESP]; Colombari, Eduardo [UNIFESP]; Sato, Monica A.; Fac Med ABC; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Ogihara CA, Schoorlemmer GHM, Levada AC, Pithon-Curi TC, Curi R, Lopes OU, Colombari E, Sato MA. Exercise changes regional vascular control by commissural NTS in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 299: R291-R297, 2010. First published April 21, 2010; doi: 10.1152/ajpregu.00055.2009.-Inhibition of the commissural nucleus of the solitary tract (commNTS) induces a fall in sympathetic nerve activity and blood pressure in spontaneously hypertensive rats (SHR), which suggests that this subnucleus of the NTS is a source of sympathoexcitation. Exercise training reduces sympathetic activity and arterial pressure. the purpose of the present study was to investigate whether the swimming exercise can modify the regional vascular responses evoked by inhibition of the commNTS neurons in SHR and normotensive Wistar-Kyoto (WKY) rats. Exercise consisted of swimming, 1 h/day, 5 days/wk for 6 wks, with a load of 2% of the body weight. the day after the last exercise session, the rats were anesthetized with intravenous alpha-chloralose, tracheostomized, and artificially ventilated. the femoral artery was cannulated for mean arterial pressure (MAP) and heart rate recordings, and Doppler flow probes were placed around the lower abdominal aorta and superior mesenteric artery. Microinjection of 50 mM GABA into the commNTS caused similar reductions in MAP in swimming and sedentary SHR (-25 +/- 6 and -30 +/- 5 mmHg, respectively), but hindlimb vascular conductance increased twofold in exercised vs. sedentary SHR (54 +/- 8 vs. 24 +/- 5%). GABA into the commNTS caused smaller reductions in MAP in swimming and sedentary WKY rats (-20 +/- 4 and -16 +/- 2 mmHg). Hindlimb conductance increased fourfold in exercised vs. sedentary WKY rats (75 +/- 2% vs. 19 +/- 3%). Therefore, our data suggest that the swimming exercise induced changes in commNTS neurons, as shown by a greater enhancement of hindlimb vasodilatation in WKY vs. SHR rats in response to GABAergic inhibition of these neurons.
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A FALL in ARTERIAL BLOOD-PRESSURE PRODUCED BY INHIBITION of the CAUDALMOST VENTROLATERAL MEDULLA - the CAUDAL PRESSER AREA
(Elsevier B.V., 1994-11-01) Possas, O. S.; Campos, R. R.; Cravo, S. L.; Lopes, O. U.; Guertzenstein, P. G.; Universidade Federal de São Paulo (UNIFESP)
The caudal edge of the ventrolateral medulla was mapped to localize sites where microinjections of L-glutamate (L-glu) produce presser responses in paralyzed and artificially ventilated urethane-anesthetized rats. Presser responses ranging from 15 to 65 mmHg were obtained when L-Glu (0.25 M, 200 nl) was microinjected in the ventral medullary surface within an area localized between the rootlets of the XII and first cervical nerves, lateral to the pyramids and just medial to the spinal roots of the XI cranial nerve. This area has been called the caudal presser area (CPA). Inhibition of the CPA by microinjection of GABA or glycine resulted in marked falls (15-45 mmHg) of arterial blood pressure (AP). Hypotension in response to CPA inhibition was also obtained in unanesthetized decerebrate animals. Cardiovascular responses to CPA stimulation or inhibition depend on the activity of neurons in the rostral ventrolateral medulla (RVLM). During hypotension provoked by RVLM inhibition, presser responses to CPA stimulation were abolished. Conversely, presser responses to RVLM stimulation were maintained during hypotension produced by inhibition of CPA, Presser response to bilateral carotid occlusion were not reduced by CPA inhibition. We conclude that cells in the caudal most ventrolateral medulla exert a tonic presser activity that contributes to maintenance of basal levels of the vasomotor tone and arterial blood pressure, its inhibition, however, does not prevent the presser response to carotid occlusion.
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GABA/benzodiazepine receptors in the ventromedial hypothalamic nucleus regulate both anxiety and panic-related defensive responses in the elevated T-maze
(Elsevier B.V., 2007-09-14) Bueno, Cintia Heloina; Zangrossi Junior, Helio; Viana, Milena de Barros [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
It has been shown that facilitation of GABA-mediated neurotransmission in the medial nucleus of the amygdala and the dorsal periaqueductal gray (dPAG) inhibits the escape, but not the inhibitory avoidance response generated in the elevated T-maze test of anxiety (ETM). These defensive behaviors have been associated with panic and generalized anxiety, respectively. Previous evidence indicates that the dorsomedial part of the ventromedial hypothalamus (VMHdm), which is interconnected with these two brain areas, is also part of the neurobiological substrate controlling escape behavior. in the present study, we investigated in male Wistar rats whether the intra-VMHdm injection of GABA-modulating drugs differently affect the two defensive tasks measured in the ETNI. the results showed that the microinjection of the benzodiazepine (BZD) receptor agonist midazolam (10, 20 and 40 nmol), the GABA(A) receptor agonist muscimol (2, 4 and 8 nmol) or the GABA(B) receptor agonist baclofen (2, 4 and 8 nmol) impaired inhibitory avoidance and escape performance, an anxiolytic and panicolytic-like effect, respectively. On the other hand, local administration of the BZD inverse agonist FG 7142 (20, 40 and 80 pmol) facilitated both behaviors, suggesting anxiogenic and panicogenic-like effects. These results were not due to motor alterations, since the drugs did not affect exploratory behavior in an open field. the data suggest that GABA(A)/BZD and GABAB receptors within the VMHdm are involved not only in the control of panic-related, but also of anxiety-related behaviors. (c) 2007 Elsevier Inc. All fights reserved.
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Inhibitory effect of GABAergic drugs in cocaine-induced genital reflexes in paradoxical sleep-deprived male rats
(Elsevier B.V., 2004-06-01) Andersen, Monica Levy [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The aim of this study was to seek whether GABAergic drugs were involved in the action of cocaine on spontaneous genital reflexes (penile erection-PE, and ejaculation-EJ) of paradoxical sleep-deprived (PSD) male rats. After a 4-day period of PSD, each group was administered with GABAergic drugs 1 h prior to cocaine and placed in observation cages. the administration of gamma-aminobutyric acid (GABA)-A agonist (muscimol, 2 and 3 mg/kg sc) reduced the number of animals displaying PE, whereas all doses tested of muscimol and bicuculline significantly reduced the frequency of PE. Pretreatment with the lower doses of GABA-B antagonist, phaclofen (1 and 2 mg/kg sc), also significantly reduced the percentage of rats showing PE; however, after the higher dose injection, the proportion of animals with PE was similar to those seen after vehicle pretreatment. Both GABA-B agonist and antagonist significantly reduced the PE frequency for all doses used compared with the vehicle group. There were no significant differences between control and GABA-A drugs in EJ behavior, whereas phaclofen 2 mg/kg pretreatment increased the ejaculatory latency. These data show that GABAergic compounds inhibited PE in male PSD rats suggesting that this inhibition points to a differential role of GABA receptor subtypes. (C) 2004 Elsevier Inc. All rights reserved.
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Inhibitory role of the zona incerta in the pilocarpine model of epilepsy
(Elsevier B.V., 2002-03-01) Hamani, C.; Sakabe, S.; Bortolotto, Z. A.; Cavalheiro, E. A.; Mello, LEAM; Universidade Federal de São Paulo (UNIFESP)
Recent experiments have suggested that the zona incerta might be regarded as a highly sensitive structure for seizure induction. This sensitivity has been linked to this structure's abundant expression of cholinergic receptors. Here we have decided to investigate the participation of the GABAergic system of the zona incerta. one of its major neurotransmitters with widespread projections to the neocortex. in the pilocarpine (Pilo) model of epilepsy. Stereotaxic administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or saline (controls) bilaterally into the zona incerta of adult male Wistar rats was performed 30 min prior to the systemic injection of pilocarpine. Animals were electroencephalographically and behaviorally monitored for seizure activity. Administration of muscimol had a pro-convulsant effect characterised by a higher percentage of animals developing SE with a shorter latency. Conversely, administration of bicuculline had a dose dependent anticonvulsant effect, with no animals displaying SE. Our results contribute to the further characterisation of the regulatory role of the zona incerta in seizure-related phenomena, suggesting that its modulation might be a relevant target for anticonvulsant strategies. (C) 2002 Published by Elsevier Science B.V.
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Learning deficits induced by sleep deprivation and recovery are not associated with altered [H-3]muscimol and [H-3]flunitrazepam binding
(Elsevier B.V., 2005-03-10) Dubiela, Francisco Paulino [UNIFESP]; Oliveira, MGM; Moreira, K. M.; Nobrega, J. N.; Tufik, S.; Hipólide, Débora Cristina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Ctr Addict & Mental Hlth
Several studies have shown that sleep deprivation produces deficits in learning tasks, but mechanisms underlying these effects remain unclear. Other lines of evidence indicate an involvement of brain GABA systems in cognitive processes. Here, we investigated the possibility that alterations in GABA(A) or benzodiazepine (BDZ) receptor binding might underlie avoidance deficits induced by sleep deprivation. Rats were deprived of sleep for 96 h using the platform method and then trained in a step-through inhibitory avoidance task, or allowed to recover sleep for 24 h before training (sleep rebound group). Thirty minutes after training, animals were given a retention test. Both sleep-deprived and sleep-recovered animals showed a significant impairment in avoidance responding compared to cage controls, and the sleep-deprived group performed significant worse than the sleep-recovered group. A separate group of animals was sacrificed either immediately after 96 h of sleep deprivation or after 96 h of sleep deprivation followed by 24 h of sleep recovery. [H-3]muscimol and [H-3]flunitrazepam binding were examined by quantitative autoradiography in 42 brain regions, including areas involved in cognitive processes. No significant differences among groups were found in any brain region, except for a reduction in [H-3]flunitrazepam binding in the frontal cortex of sleep-recovered animals. These results confirm the deleterious effects of sleep loss on inhibitory avoidance learning, but suggest that such deficits cannot be attributed to altered GABA(A) or BDZ binding in brain. (c) 2005 Elsevier B.V. All rights reserved.
Somente Metadadados
Low ethanol concentrations selectively augment the tonic inhibition mediated by delta subunit-containing GABA(A) receptors in hippocampal neurons
(Soc Neuroscience, 2004-09-22) Wei, Weizheng Z.; Faria, Leonardo Coutinho [UNIFESP]; Mody, Istvan; Univ Calif Los Angeles; Universidade Federal de São Paulo (UNIFESP)
In central neurons, a tonic conductance is activated by ambient levels of the inhibitory transmitter GABA. Here, we show that in dentate gyrus granule cells, where tonic inhibition is mediated by delta subunit-containing GABA(A) receptors, this conductance is augmented by low concentrations (30 mM) of ethanol. in contrast, the tonic inhibition mediated by alpha5 subunit-containing receptors of CA1 pyramidal cells is not affected. the effect of ethanol on tonic inhibition specifically reduces the excitability of the dentate gyrus and identifies the delta subunit-dependent tonic inhibition as a likely site of ethanol action in the brain.
Acesso aberto (Open Access)
Microinjection of GABAergic agents into the anterior nucleus of the thalamus modulates pilocarpine-induced seizures and status epilepticus
(W B Saunders Co Ltd, 2010-05-01) Bittencourt, Simone [UNIFESP]; Dubiela, Francisco Paulino [UNIFESP]; Queiroz, Claudio Marcos [UNIFESP]; Covolan, Luciene [UNIFESP]; Andrade, Danielle; Lozano, Andres; Mello, Luiz Eugenio Araujo de Moraes [UNIFESP]; Hamani, Clement [UNIFESP]; Toronto Western Hosp; Universidade Federal de São Paulo (UNIFESP)
The anterior nucleus of the thalamus (AN) has been suggested as a potential target for seizure modulation in animal models and patients with refractory epilepsy. We investigate whether microinjections of GABAergic agonists into the AN were protective against pilocarpine-induced generalized seizures and status epilepticus (SE). Rats were treated with bilateral AN injections of muscimol (160 or 80 nmol), bicuculline (15 nmol), or saline (controls) 20 min prior to pilocarpine administration (350 mg/kg i.p.). Electrographic recordings were used to confirm seizure activity. We found that pretreatment with AN muscimol 160 nmol increased the latency to seizures and SE by 2.5-3.0-fold. This dose however was associated with side effects, particularly hypotonia. AN bicuculline was proconvulsant, whereas no major effect was observed after muscimol 80 nmol injections. the percentage of animals that developed SE was similar across groups. Overall, microinjection of high doses of muscimol into the AN delayed the occurrence of pilocarpine-induced seizures and SE but was not able to prevent these events. (C) 2010 British Epilepsy Association. Published by Elsevier B.V. All rights reserved.
Somente Metadadados
MODULATION of HALOPERIDOL-INDUCED CATALEPSY in RATS BY GABAERGIC NEURAL SUBSTRATE in the INFERIOR COLLICULUS
(Elsevier B.V., 2013-12-26) Tostes, J. G.; Medeiros, P. [UNIFESP]; Melo-Thomas, L. [UNIFESP]; Univ Sao Francisco; Fac Med Itajuba; Universidade Federal de São Paulo (UNIFESP); Inst Neurociencias & Comportamento INEC
Not only is the inferior colliculus (IC) a highly important center of integration within the central auditory pathway, but it may also play a modulatory role in sensorymotor circuitry. Previous evidence from our laboratory relating the IC to motor behavior shows that glutamate-mediated mechanisms within the IC modulate haloperidol-induced catalepsy. the high density of GABAergic receptors in the IC led to this study of a possible link between these receptors, haloperidol-induced catalepsy, and a possible involvement of the blockade of dopaminergic receptors. Catalepsy was evaluated by positioning both forepaws of rats on an elevated horizontal wooden bar and recording the time that the animal maintained this position. the present study shows that haloperidol-induced catalepsy was enhanced by local microinjection into the IC of midazolam (20 nmol/0.5 mu l), a benzodiazepine receptor agonist, whereas animals receiving a microinjection of bicuculline (40 or 80 ng/0.5 mu l), a GABAergic antagonist, showed a reduction in the time of catalepsy. However, the microinjection of haloperidol (2.5 or 5.0 mu g/0.5 mu l) bilaterally into the IC did not induce catalepsy. Therefore, our results suggest the involvement of the IC in the modulation of catalepsy induced by haloperidol, even though the dopaminergic mechanisms of the IC are unable to induce catalepsy when blocked by the direct microinjection of haloperidol. It is thus possible that the IC plays a role in sensorimotor gating and that GABA-mediated mechanisms are involved. (C) 2013 IBRO. Published by Elsevier B.V. All rights reserved.

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