Role of dopaminergic D2 receptors in regulating molecular biomarkers os neural lasticity and memory consolidation

• Autor(a) principal: Aguiar, L. M.
• Data de Publicação: 2011
• Outros Autores: Soares, B. L., França, A. S. C., Nascimento, G. C. D., Ribeiro, Sidarta Tollendal Gomes
• Tipo de documento: Artigo de conferência
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRN
• Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/24381
• topic: Dopamine; Memory consolidation; Synaptic plasticity; Sleep

Objectives: To investigate whether the D2 antagonist haloperidol can modulate the hippocampal expression levels of Zif-268 and phosphorylated CaMKII, two synaptic plasticity biomarkers related to memory consolidation. Methods and Results: For memory consolidation analysis, male adult mice (Mus musculus, 19-29g) separated in two groups (haloperidol 0.3 mg/kg - HALO i.p. and vehicle, n=8 per group) were submitted to two sessions of object exploration with a 24 hours inter-session interval. Drugs were injected i.p. immediately after the first exploration session. An object recognition index (exploration time of unfamiliar/ familiar objects) was obtained in the second object exploration session. The HALO group presented a significant decrease in object recognition when compared to vehicle (respectively 1.51 ± 0.11 and 2.5 ± 0.19; p=0.0007). In a separate group of animals (n=10 for HALO and 11 for vehicle), the brains were removed three hours after a single session of object exploration, and the tissue was processed for immunohistochemistry of Zif-268 and phosphorilated CaMKII. Zif-268 expression was quantified by counts of positively-labeled nuclei, and CamKII phosphorylation was quantified by densitometry, with measurements taken from the hippocampal regions CA1, CA3 and dentate gyrus. We performed student t tests for comparisons between the two groups, and the significance level was set at 0.05. No significant difference related to Zif-268 expression was observed. On the other hand, a significant reduction in CaMKII phosphorylation in the CA1 region was observed in the HALO group, when compared to the vehicle group (0.84 ± 0.05 and 1.14 ± 0.1; p=0.016). Conclusions: These results suggest that the blockade of D2 receptors can impair mnemonic systems, leading to both a decrease in the phosphorylation of CAMKII, and to behavioral changes that indicate learning impairment.