Ultra-low exposure to alpha-7 nicotinic acetylcholine receptor partial agonists elicits an improvement in cognition that corresponds with an increase in alpha-7 receptor expression in rodents: implications for low dose clinical efficacy

• Published in: Neuroscience Vol. 186; pp. 76 - 87
• Main Authors: Werkheiser, J.L, Sydserff, S, Hubbs, S.J, Ding, M, Eisman, M.S, Perry, D, Williams, A.J, Smith, J.S, Mrzljak, L, Maier, D.L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 14.07.2011; Elsevier
• Subjects: [ 125I]-α-bungarotoxin; [ 3H]AZ11637326; alpha7 Nicotinic Acetylcholine Receptor; Animals; AZD0328; Biological and medical sciences; Brain - drug effects; Brain - physiology; Cognition - drug effects; Cognition - physiology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; in vivo and ex vivo receptor binding; Male; Mice; Mice, Inbred C57BL; Neurology; Nicotinic Agonists - pharmacology; Nootropic Agents - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology; SSR180711; Vertebrates: nervous system and sense organs; α7 neuronal nicotinic receptor; multiple reaction monitoring; alpha-7 neuronal nicotinic acetylcholine receptor; [ 125I]-α-bungarotoxin; α7 neuronal nicotinic receptor; LTP; MRM; AZD0328; intrinsic activity; receptor affinity; K d; in vivo and ex vivo receptor binding; [ 3H]AZ11637326; receptor number; α7 NNR; B max; EC 50; SSR180711; long-term potentiation; Agonist; Rodentia; Cognition; I]-α-bungarotoxin; Vertebrata; Cholinergic receptor; H]AZ11637326; Mammalia; α7 nicotinic receptor; [; Nicotinic receptor; Biological receptor

Abstract Αlpha-7 neuronal nicotinic receptors (NNRs) are considered targets for cognitive enhancement in schizophrenia and Alzheimer's disease. AZD0328 is an alpha-7 NNR partial agonist that enhances cognition in rodents and nonhuman primates at sub-microgram to microgram doses. We hypothesized...