title: Restoration of dopamine release deficits during object recognition memory acquisition attenuates cognitive impairment in a triple transgenic mice model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México D.F., Mexico.
authors.forename: Kioko
authors.initials: K
authors.lastname: Guzmán-Ramos
authors.forename: Perla
authors.initials: P
authors.lastname: Moreno-Castilla
authors.forename: Monica
authors.initials: M
authors.lastname: Castro-Cruz
authors.forename: James L
authors.initials: JL
authors.lastname: McGaugh
authors.forename: Hilda
authors.initials: H
authors.lastname: Martínez-Coria
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
authors.forename: Federico
authors.initials: F
authors.lastname: Bermúdez-Rattoni
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis; D009154:Mutation / Q000235:genetics; D009627:Nomifensine / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D010775:Photic Stimulation; D053764:Presenilin-1 / Q000235:genetics; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018765:Dopamine Uptake Inhibitors; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins; D009627:Nomifensine; D018698:Glutamic Acid; D004298:Dopamine; D009638:Norepinephrine