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Science 13 December 1985:
Vol. 230. no. 4731, pp. 1273 - 1276
DOI: 10.1126/science.2999977
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Articles

Science, Vol 230, Issue 4731, 1273-1276
Copyright © 1985 by American Association for the Advancement of Science

articles

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

AF Arnsten and PS Goldman-Rakic

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pre- and Postsynaptic {beta}-Adrenergic Activation Enhances Excitatory Synaptic Transmission in Layer V/VI Pyramidal Neurons of the Medial Prefrontal Cortex of Rats.
X.-H. Ji, X.-H. Cao, C.-L. Zhang, Z.-J. Feng, X.-H. Zhang, L. Ma, and B.-M. Li (2008)
Cereb Cortex 18, 1506-1520
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Role of the Lateral Prefrontal Cortex in Executive Behavioral Control.
J. Tanji and E. Hoshi (2008)
Physiol Rev 88, 37-57
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Catecholamine and Second Messenger Influences on Prefrontal Cortical Networks of "Representational Knowledge": A Rational Bridge between Genetics and the Symptoms of Mental Illness.
A. F. T. Arnsten (2007)
Cereb Cortex 17, i6-i15
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Molecular activity underlying working memory.
P. K. Dash, A. N. Moore, N. Kobori, and J. D. Runyan (2007)
Learn. Mem. 14, 554-563
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{alpha}2A-adrenoceptor stimulation improves prefrontal cortical regulation of behavior through inhibition of cAMP signaling in aging animals.
B. P. Ramos, D. Stark, L. Verduzco, C. H. van Dyck, and A. F.T. Arnsten (2006)
Learn. Mem. 13, 770-776
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Noradrenaline and Dopamine Elevations in the Rat Prefrontal Cortex in Spatial Working Memory.
Z. L. Rossetti and S. Carboni (2005)
J. Neurosci. 25, 2322-2329
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Estrogen Replacement Increases Spinophilin-immunoreactive Spine Number in the Prefrontal Cortex of Female Rhesus Monkeys.
Y. Tang, W. G.M. Janssen, J. Hao, J. A. Roberts, H. McKay, B. Lasley, P. B. Allen, P. Greengard, P. R. Rapp, J. H. Kordower, et al. (2004)
Cereb Cortex 14, 215-223
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Executive Control Function: A Review of Its Promise and Challenges for Clinical Research. A Report From the Committee on Research of the American Neuropsychiatric Association.
D. R. Royall, E. C. Lauterbach, J. L. Cummings, A. Reeve, T. A. Rummans, D. I. Kaufer, W. C. LaFrance Jr., and C. E. Coffey (2002)
J Neuropsychiatry Clin Neurosci 14, 377-405
   Abstract »    Full Text »    PDF »
Mutation of the alpha 2A-Adrenoceptor Impairs Working Memory Performance and Annuls Cognitive Enhancement by Guanfacine.
J. S. Franowicz, L. E. Kessler, C. M. D. Borja, B. K. Kobilka, L. E. Limbird, and A. F. T. Arnsten (2002)
J. Neurosci. 22, 8771-8777
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Differential Effects of 6-OHDA Lesions of the Frontal Cortex and Caudate Nucleus on the Ability to Acquire an Attentional Set.
H.S. Crofts, J.W. Dalley, P. Collins, J.C.M. Van Denderen, B.J. Everitt, T.W. Robbins, and A.C. Roberts (2001)
Cereb Cortex 11, 1015-1026
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Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain.
M. A. Mehta, A. M. Owen, B. J. Sahakian, N. Mavaddat, J. D. Pickard, and T. W. Robbins (2000)
J. Neurosci. 20, RC65
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Attenuation of Delay-Period Activity of Monkey Prefrontal Neurons by an alpha 2-Adrenergic Antagonist During an Oculomotor Delayed-Response Task.
T. Sawaguchi (1998)
J Neurophysiol 80, 2200-2205
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alpha 2C-Adrenoceptor-Overexpressing Mice Are Impaired in Executing Nonspatial and Spatial Escape Strategies.
M. Björklund, J. Sirviö, J. Puoliväli, J. Sallinen, P. Jäkälä, M. Scheinin, B. K. Kobilka, and P. Riekkinen Jr. (1998)
Mol. Pharmacol. 54, 569-576
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Noise Stress Impairs Prefrontal Cortical Cognitive Function in Monkeys: Evidence for a Hyperdopaminergic Mechanism.
A. F. T. Arnsten and P. S. Goldman-Rakic (1998)
Arch Gen Psychiatry 55, 362-368
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Stimulation and blockade of {alpha}1 adrenoceptors affect behavioural activity, but not spatial working memory assessed by delayed non-matching to position task in rats.
T. Puumala and J. Sirvio (1997)
J Psychopharmacol 11, 45-51
   Abstract »    PDF »
Catecholamine regulation of the prefrontal cortex.
A. F. T. Arnsten (1997)
J Psychopharmacol 11, 151-162
   Abstract »    PDF »
The Contribution of {alpha}2-Noradrenergic Mechanisms to Prefrontal Cortical Cognitive Function: Potential Significance for Attention-Deficit Hyperactivity Disorder.
A. F.T. Arnsten, J. C. Steere, and R. D. Hunt (1996)
Arch Gen Psychiatry 53, 448-455
   Abstract »    PDF »
Sensorimotor Gating and Schizophrenia: Human and Animal Model Studies.
D. L. Braff and M. A. Geyer (1990)
Arch Gen Psychiatry 47, 181-188
   Abstract »    PDF »
Clonidine Treatment of Alzheimer's Disease.
E. Mohr, J. Schlegel, G. Fabbrini, J. Williams, M. M. Mouradian, U. M. Mann, J. J. Claus, P. Fedio, and T. N. Chase (1989)
Arch Neurol 46, 376-378
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