Papel do bloqueio dos receptores NMDA e da ativação dos receptores GABAA na manifestação dos déficits neurocomportamentais decorrentes da exposição ao etanol durante o período equivalente ao terceiro trimestre de gestação

• Autor(a) principal: Pinto, Juliana de Oliveira
• Data de Publicação: 2012
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12781
• topic: NMDA receptors; GABAA receptors; Locomotor activity; Learning and memory; Receptores NMDA; Receptores GABAA; Atividade Locomotora; Aprendizado e Memória; Etanol Efeitos adversos; Transtorno do Deficit de Atenção com Hiperatividade; Transtornos Relacionados ao Uso de Álcool; Receptores de N-Metil-D-Aspartato; Receptores de ácido gam-aminobutírico; Atividade motora; Transtornos de memória; Transtornos de aprendizagem; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS::NEUROFISIOLOGIA

Gestational exposure to ethanol results in a broad spectrum of behavioral deficits that can last for the entire life of the individual. Among the most common observed alterations are the attention deficit and hyperactive disorder (ADHT) and learning and memory deficits. In spite of the many studies that are available, the mechanisms associated with the manifestation of these disorders remain, for the most part, unknown. Studies carried out in rodents have been demonstrating that the period equivalent to the third trimester of human gestation is particularly critical for the development of these behavioral alterations. During this period, which is characterized by intense synaptogenesis, the ethanol neurotoxicity has been attributed to the blockage of the N-methyl-D-aspartate (NMDA) glutamatergic receptors and to the overactivation of the A subtype of the gamma-aminobutyric acid (GABAA). Considering that throughout development differ regarding function and spatio-temporal distribution, in the present study we evaluated the relative contribution of NMDA receptor blockage and overactivation of GABAA receptors during the third trimester equivalent period regarding the manifestation of locomotor hyperactivity and of memory/learning deficits in prepubertal mice. The study was carried out in two separate parts. In the first part, we investigated the effects of isolated exposure to MK801 (MK), a NMDA blocker and to muscimol (MU), a GABAA agonist. To that effect, from the 2nd postnatal (PN) day to PN8 the animals received, every other day, an i.p. injection of either saline solution (SAL) or MK (doses: 0.1, 0.3 or 0.5 mg/kg) or MU (doses: 0.1, 0.3 or 0,5 mg/kg). In the second part of the study we investigated the effects of a simultaneous injection of MK (0.1 mg/kg) and MU (doses: 0.02, 0.1 or 0.5 mg/kg). At PN25, the locomotor activity was automatically assessed for 15 min in the open field test. At PN31 and PN32, learning and memory performance were assessed in the inhibitory passive avoidance test. Regarding the results of the isolated exposure to each of the drugs, only the treatment with MK promoted a dose-dependent increase in locomotor activity. In the passive avoidance test, the animals exposed to the higher doses of MK and MU presented learning and memory deficits. Regarding the results of the combined exposure to MK and MU, no significant differences were observed between groups in locomotor activity. In the passive avoidance test, the simultaneous injection of MK and MU, at doses that when administered separately did not have any effect, caused learning and memory deficits. Our results suggest that, while locomotor activity is associated only with NMDA receptor blockage, learning and memory deficits may be the result of a synergistic action of ethanol on both receptors.