Efeitos das infusões de muscimol e AP5 no subículo dorsal sobre a aquisição e a consolidação do condicionamento de medo ao contexto em ratos

• Ano de defesa: 2019
• Autor(a) principal: Braga de Melo, Márcio [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Contextual fear conditioning; N-methyl D-Aspartate; Muscimol; Subiculum; Subículo; Condicionamento de medo ao contexto; NMDA; Esquiva inibitória step-through
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7830892; https://repositorio.unifesp.br/handle/11600/58747

The dorsal hippocampus (DH) has a well-known role in the contextual fear conditioning (CFC) and spatial information. Involvement of the DH in CFC has been established by showing that its muscimol-induced temporary inactivation impairs CFC consolidation while acquisition is hindered by blocking DH glutamatergic NMDA receptors with AP5. The dorsal subiculum (DSub) is also involved in spatial information and it is necessary for retrieval of the CFC. Moreover, the DSub is a major output from the hippocampus through pathways that seemingly relies on NMDA-dependent synaptic plasticity. However, the implication of the DSub in the CFC consolidation is still unclear. Our aim was to assess the effects of intra-DSub muscimol or AP5 infusion on CFC acquisition and consolidation. The DSub of 3-to-4-month-old male Wistar rats were bilaterally cannulated (AP=-6.4 mm, ML=±3.8 mm, DV=- 3.4 mm). CFC training consisted of applying a footshock (1s/0.8mA – after a 120s delay) as the unconditioned stimulus. A 5-min test was done 48h later, and freezing was assessed as the behavioral conditioned response. All groups received 0.2ul/hemisphere infusions 5min before or immediately after the training. Data from animals with incorrect cannula implantation were excluded. To control for bias such as shock sensitivity and emotional reaction, we employed a hippocampal-independent procedure: step-through inhibitory avoidance (ST IA). Freezing was analyzed by the generalized estimating equations (GEE) method, with group and time-bin (minute-by-minute) as independent factors. IAST latency was analyzed by generalized linear model (GzLM), with group as the only independent factor. LSD posthoc test was applied when appropriate. The pre or posttraining intra-DSub muscimol infusion impairs the CFC. The pre-training intra-DSub AP5 infusion did not impair CFC, but the post-training manipulation did. Our data, together with the literature, suggest that the integrity of the DSub, as structure, is necessary only for the CFC consolidation. Furthermore, the NMDA receptors in this region are also necessary for the consolidation, but not for the CFC acquisition, a different pattern from the observed in the DH. The lack of drug effect on ST IA latency indicates that controlled factors did not account for the observed differences.