Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates.

This study provides evidence that the alpha 2-adrenergic receptor agonist clonidine ameliorates the cognitive deficits exhibited by aged nonhuman primates through drug actions at alpha 2 receptors. Furthermore, pharmacological profiles in animals with lesions restricted to the dorsolateral prefrontal cortex indicate that this area may be the site of action for some of clonidine's beneficial effects. These results demonstrate that alpha-adrenergic systems contribute to cognitive function and suggest a new strategy for treating memory disorders in aged humans.

[1]  J. D. McGaugh.  Peripheral and Central Adrenergic Influences on Brain Systems Involved in the Modulation of Memory Storage a , 1985, Annals of the New York Academy of Sciences.

[2]  P. Goldman-Rakic,et al.  Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey , 1984, Brain Research.

[3]  T. Crow,et al.  Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type , 1984, Journal of the Neurological Sciences.

[4]  F. E. Bloom,et al.  Loss of pigmented dopamine-β-hydroxylase positive cells from locus coeruleus in senile dementia of alzheimer's type , 1983, Neuroscience Letters.

[5]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[6]  J. Coyle,et al.  Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. , 1982, Science.

[7]  D. Neary,et al.  ALZHEIMER'S DISEASE AS A DISORDER OF ISODENDRITIC CORE , 1982, The Lancet.

[8]  E. Perry,et al.  Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease , 1981, Journal of the Neurological Sciences.

[9]  G. Blessed,et al.  Cell loss in the locus coeruleus in senile dementia of Alzheimer type , 1981, Journal of the Neurological Sciences.

[10]  P. Goldman-Rakic,et al.  Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys , 1981, Neuroscience.

[11]  J. Ferguson,et al.  Physostigmine and Arecoline: Effects of Intravenous Infusions in Alzheimer Presenile Dementia , 1981, British Journal of Psychiatry.

[12]  S. Grant,et al.  Benzodiazepines attenuate single unit activity in the locus coeruleus. , 1980, Life sciences.

[13]  R. Mair,et al.  Memory enhancement in Korsakoff's psychosis by clonidine: Further evidence for a noradrenergic deficit , 1980, Annals of neurology.

[14]  B. Winblad,et al.  Changes in the Brain Catecholamines in Patients with Dementia of Alzheimer Type , 1979, British Journal of Psychiatry.

[15]  H. E. Rosvold,et al.  Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. , 1979, Science.

[16]  S. Snyder,et al.  Multiple apparent alpha-noradrenergic receptor binding sites in rat brain: effect of 6-hydroxydopamine. , 1979, Molecular pharmacology.

[17]  H R Johnson,et al.  Aging in the rhesus monkey: debilitating effects on short-term memory. , 1978, Journal of gerontology.

[18]  P. Davies,et al.  SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE , 1976, The Lancet.

[19]  H. E. Rosvold,et al.  Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. , 1971, Journal of comparative and physiological psychology.

[20]  H. E. Rosvold,et al.  Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey. , 1970, Experimental neurology.

[21]  C. Finch,et al.  Age-related changes in brain catecholamines: a synopsis of findings in C57BL/6J mice and other rodent models. , 1978, Advances in experimental medicine and biology.