Análise dos efeitos do extrato padronizado de Ginkgo biloba L. na aquisição e na extinção do medo condicionado
Nenhuma Miniatura disponível
Data
2013-04-25
Autores
Zamberlam, Claudia Raquel [UNIFESP]
Orientadores
Cerutti, Suzete Maria [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
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.
Previous data from our laboratory showed that the treatments in the short or long term with the standardized extract of Ginkgo biloba L. (EGb) modulates the acquisition of Emotional Response Condicionda (REC). These changes were associated with increased gene and protein expression of CREB-1 and GFAP and reduced GAP-43 in rat hippocampus and in parallel to the changes observed in the prefrontal cortex and amygdaloid complex. Understanding the cellular and molecular mechanisms underlying these processes may help in understanding the effects of EGb on the central nervous system. Several studies have suggested that glutamatergic, GABAergic and serotonergic neurotransmission systems are major strategic targets to participate in the formation of conditioned fear memory. To understand the contribution of the different systems in the stage of formation of the memory of fear conditioning, the animals were randomly divided into four groups according to the time administration of the substances, in order to evaluate the acquisition (Group 1) and recall from the fear conditioning (Group 2) or the acquisition (Group 3) and recall of extinction (Group 4) through the REC test. Group 1 (1A-D, n = 20/group) received the drugs before the acquisition of REC (Training 1, Tr1), and half (n = 10/group) of the animals were euthanized after Test 1 (T1) and the other after Test 2 (T2), in group 2 (n = 10/group) the drug was administered before Test1 (T1) and the animals were euthanized 3 or 24 hours after the end of T1, group 3 (n = 10/group) received drugs before extinction training (Training 2, Tr2) and was euthanized after 3 or 24 hours, and group 4 (n = 10/group) drugs were administered before T2 and animals were sacrificed 3 or 24 h after. Treatment with a single dose of EGb (250 mg.Kg-1 , 500 mg.Kg-1 or 1000 mg.Kg-1 ), specific antagonists of glutamatergic NMDA NR2B receptor -(RO 256981, 10 mg.Kg -1 ), GABAA type (Picrotoxin, 0,75 mg.Kg-1 ) and the serotonin 5-HT1A type (SWAY 100135, 0,3 mg.Kg-1 ) or agonists (NMDA, Diazepam and Buspirone), and vehicle solutions (Tween or saline) were administered 30 or 20 min before the experimental session, respectively. Rats treated with EGb + antagonists received drugs 50 min before the session. Analysis of the suppression rate of licking response (RS) shows that rats treated with EGb at a dose of 250 mg.Kg-1 before Tr1 and the dose of 1000 mg.Kg-1 before Tr2 had a higher suppression of lick response, compared to positive control groups (Diazepam 10 mg.Kg-1 ) and negative (Tween 80-12%) (P <0,05), favoring the acquisition of extinction of conditioned fear memory. Data obtained with the administration of antagonists suggests that EGb modulates the acquisition of conditioned fear through the NR2B receptor and 5-HT1A receptors at doses of 250 mg.Kg-1 and 500 mg.Kg-1 and reduces the deletion in 1000 mg.kg-1 via the GABAA receptor. Still, at the highest dose EGb favors the spontaneous recovery of conditioned fear when administered before training and before extinction test. Together the data shows the effects of EGb in the memory formation of conditioned fear and evidence the neurochemical mechanisms which are involved in each step.
Previous data from our laboratory showed that the treatments in the short or long term with the standardized extract of Ginkgo biloba L. (EGb) modulates the acquisition of Emotional Response Condicionda (REC). These changes were associated with increased gene and protein expression of CREB-1 and GFAP and reduced GAP-43 in rat hippocampus and in parallel to the changes observed in the prefrontal cortex and amygdaloid complex. Understanding the cellular and molecular mechanisms underlying these processes may help in understanding the effects of EGb on the central nervous system. Several studies have suggested that glutamatergic, GABAergic and serotonergic neurotransmission systems are major strategic targets to participate in the formation of conditioned fear memory. To understand the contribution of the different systems in the stage of formation of the memory of fear conditioning, the animals were randomly divided into four groups according to the time administration of the substances, in order to evaluate the acquisition (Group 1) and recall from the fear conditioning (Group 2) or the acquisition (Group 3) and recall of extinction (Group 4) through the REC test. Group 1 (1A-D, n = 20/group) received the drugs before the acquisition of REC (Training 1, Tr1), and half (n = 10/group) of the animals were euthanized after Test 1 (T1) and the other after Test 2 (T2), in group 2 (n = 10/group) the drug was administered before Test1 (T1) and the animals were euthanized 3 or 24 hours after the end of T1, group 3 (n = 10/group) received drugs before extinction training (Training 2, Tr2) and was euthanized after 3 or 24 hours, and group 4 (n = 10/group) drugs were administered before T2 and animals were sacrificed 3 or 24 h after. Treatment with a single dose of EGb (250 mg.Kg-1 , 500 mg.Kg-1 or 1000 mg.Kg-1 ), specific antagonists of glutamatergic NMDA NR2B receptor -(RO 256981, 10 mg.Kg -1 ), GABAA type (Picrotoxin, 0,75 mg.Kg-1 ) and the serotonin 5-HT1A type (SWAY 100135, 0,3 mg.Kg-1 ) or agonists (NMDA, Diazepam and Buspirone), and vehicle solutions (Tween or saline) were administered 30 or 20 min before the experimental session, respectively. Rats treated with EGb + antagonists received drugs 50 min before the session. Analysis of the suppression rate of licking response (RS) shows that rats treated with EGb at a dose of 250 mg.Kg-1 before Tr1 and the dose of 1000 mg.Kg-1 before Tr2 had a higher suppression of lick response, compared to positive control groups (Diazepam 10 mg.Kg-1 ) and negative (Tween 80-12%) (P <0,05), favoring the acquisition of extinction of conditioned fear memory. Data obtained with the administration of antagonists suggests that EGb modulates the acquisition of conditioned fear through the NR2B receptor and 5-HT1A receptors at doses of 250 mg.Kg-1 and 500 mg.Kg-1 and reduces the deletion in 1000 mg.kg-1 via the GABAA receptor. Still, at the highest dose EGb favors the spontaneous recovery of conditioned fear when administered before training and before extinction test. Together the data shows the effects of EGb in the memory formation of conditioned fear and evidence the neurochemical mechanisms which are involved in each step.
Descrição
Citação
ZAMBERLAM, Claudia Raquel. Análise dos efeitos do extrato padronizado de Ginkgo biloba L. na aquisição e na extinção do medo condicionado. 2013. 92 f. Dissertação (Mestrado) - Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo (UNIFESP), Diadema, 2013.