Cognitive impairment in aged rhesus monkeys associated with monoamine receptors in the prefrontal cortex.
The "frontal aging hypothesis" has been proposed by many researchers suggesting that the earliest and most severe age-related changes in the cortex occur in the frontal lobes. Two of these changes include decreases in cognitive functions mediated by the prefrontal cortex (PFC) and significant decreases in norepinephrine (NE) and dopamine (DA). To investigate whether the changes in these neurotransmitter systems are directly related to the cognitive decline seen in aging we utilized the rhesus monkey as a model of normal human aging. Our goal was to determine if age-related changes in cognition is associated with changes in norepinephrine and dopamine receptor binding density in the PFC. Eight young monkeys between five and ten years of age (six males and two female) and eight aged monkeys between 25 and 32 years of age (five males and three females) were behaviorally characterized. Subsequently on-the-slide in vitro binding assays were used to quantify the alpha-1 adrenergic, alpha-2 adrenergic and DA1 receptors as well as the NE and DA uptake receptors. Aged animals as a group demonstrated significant cognitive impairments and aging produced a significant decrease in alpha-1 adrenergic and alpha-2 adrenergic receptor binding in the PFC but no significant change in binding for the DA1 receptor or the NE or DA uptake receptors. Further analysis revealed a significant relationship between monoamine receptor binding and cognitive performance on three tasks: delayed non-matching to sample, delayed recognition span test and the conceptual set-shifting task.
Moore
Tara L
TL
Department of Anatomy and Neurobiology, Boston University School of Medicine, MA 02118, USA. tlmoore@bu.edu
Schettler
Stephen P
SP
Killiany
Ronald J
RJ
Herndon
James G
JG
Luebke
Jennifer I
JI
Moss
Mark B
MB
Rosene
Douglas L
DL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D001552:Benzazepines / Q000494:pharmacology; D001931:Brain Mapping; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology; D004193:Discrimination Learning / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009483:Neuropsychological Tests; D011224:Prazosin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000378:metabolism*; D011869:Radioligand Assay / Q000379:methods; D017983:Receptors, Catecholamine / Q000145:classification / Q000378:metabolism*; D013223:Statistics as Topic; D014316:Tritium / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D018492:Dopamine Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017983:Receptors, Catecholamine; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D003000:Clonidine; D011224:Prazosin