RESUMO

Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo microdialysis, cortical and hippocampal dopamine, norepinephrine, and glutamate release during the acquisition of object recognition memory (ORM) in 5- and 10-mo-old triple-transgenic Alzheimer's disease mice (3xTg-AD) and to relate the extracellular changes to 24-h memory performance. Five- and 10-mo-old wild-type mice and 5-mo-old 3xTg-AD showed significant cortical but not hippocampal dopamine increase during object exploration. On a 24-h ORM test, these three groups displayed significant ORM. In contrast, 10-mo-old 3xTg-AD mice showed impaired dopamine release in the insular cortex during ORM acquisition, as well as significant impairment in ORM. In addition, cortical administration of a dopamine reuptake blocker produced an increase of dopamine levels in the 10-mo-old 3xTg-AD mice and attenuated the memory impairment. These data suggest that activation of the dopaminergic system in the insular cortex is involved in object recognition memory, and that dysfunction of this system contributes to the age-related decline in cognitive functioning of the 3xTg-AD mice.

Assuntos

Encéfalo , Transtornos Cognitivos/metabolismo , Dopamina/metabolismo , Transtornos da Memória/metabolismo , Reconhecimento Psicológico/fisiologia , Fatores Etários , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Modelos Animais de Doenças , Inibidores da Captação de Dopamina/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Ácido Glutâmico/metabolismo , Humanos , Masculino , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microdiálise , Mutação/genética , Nomifensina/uso terapêutico , Norepinefrina/metabolismo , Estimulação Luminosa , Presenilina-1/genética , Reconhecimento Psicológico/efeitos dos fármacos , Estatísticas não Paramétricas , Proteínas tau/genética , Proteínas tau/metabolismo