Aged dogs demonstrate both increased sensitivity to scopolamine impairment and decreased muscarinic receptor density.
Memory deficits associated with aging and Alzheimer's disease have been linked to cholinergic dysfunction. The present study investigated this hypothesis by comparing the effects of the muscarinic cholinergic receptor antagonist scopolamine on recent memory performance and by examining muscarinic receptor density in aged and young dogs. Scopolamine (15 μg/kg; SC) was administered prior to testing young (M=2.8 years) and aged (M=13.0 years) dogs on a delayed-non-matching-to-position task (DNMP). Scopolamine significantly impaired performance of aged, but not young dogs. Muscarinic receptor density was assessed autoradiographically using the non-selective radioligand [(3)H]quinuclidinylbenzilate. Aged dogs (M=14.1 years) showed significantly decreased density of muscarinic receptors in all brain regions examined except the cerebellum compared to young dogs (M=3.7 years). The results are consistent with those seen in aged humans and Alzheimer's patients and support the hypothesis of age-dependent cholinergic dysfunction in the dog, although this was not directly determined in the current study. These findings demonstrate that markers of cholinergic hypofunction, in addition to the natural cognitive decline and amyloid pathology previously noted, are seen in canine aging. Collectively, this supports the use of the aged dog as a model for examining early pathological events in the development of Alzheimer's disease.
Department of Pharmacology, University of Toronto, Toronto, Canada. josepha@cancog.com
Joseph A
JA
Araujo
José N
JN
Nobrega
Roger
R
Raymond
Norton W
NW
Milgram
D000375:Aging / Q000502:physiology* / Q000523:psychology*; D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology*; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology*; D014018:Tissue Distribution
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012601:Scopolamine