Glucose attenuates impairments in memory and CREB activation produced by an α4β2 but not an α7 nicotinic receptor antagonist

NEUROPHARMACOLOGY

卷:67

Article

Morris, Ken A.¹  Li, Sisi²  Bui, Duat D.²  Gold, Paul E.³ 

[1] Univ Illinois, Coll Med, Neurosci Program, Champaign, IL USA

[2] Univ Illinois, Sch Mol & Cellular Biol, Champaign, IL USA

[3] Syracuse Univ, Dept Biol, Syracuse, NY 13244 USA

关键词: Glucose;    Memory;    Acetylcholine;    Nicotinic;    alpha 4 beta 2 receptor;    alpha 7 receptor;   

DOI  :  10.1016/j.neuropharm.2012.11.008

来源: Elsevier

【 摘 要 】

Glucose improves memory for a variety of tasks when administered to rats and mice near the time of training. Prior work indicates glucose may enhance memory by increasing the synthesis and release of the neurotransmitter acetylcholine in the brain. To investigate if specific acetylcholine receptor subtypes may mediate some of the memory-enhancing actions of glucose, we examined the effects of subtype-specific nicotinic acetylcholine receptor antagonists on memory in Fischer-344 rats and also examined the ability of glucose to reverse drug-induced impairments. Pre-training peripheral injections of methyllycaconitine (MLA) or dihydro-beta-erythroidine (DH beta E), which are specific alpha 7 and alpha 4 beta 2 nicotinic receptor antagonists, respectively, dose-dependently impaired retention latencies in an inhibitory avoidance task when tested 7-days but not 1 h after training. Immediate post-training glucose injections attenuated the impairments, but were more effective in attenuating the DH beta E-induced impairments. Likewise, peripheral or direct intrahippocampal injections of MLA or DH beta E dose-dependently impaired spatial working memory scores on a spontaneous alternation task. Concurrent administration of glucose reversed DH beta E- but not MLA-induced impairments. CREB phosphorylation downstream of cholinergic signaling was assessed 30 mm after spontaneous alternation testing and intrahippocampal drug infusions. Both MLA and DH beta E impaired hippocampal CREB phosphorylation; glucose reversed DH beta E- but not MLA-induced deficits. The effectiveness of glucose in reversing DH beta E- but not MLA-induced impairments in behavioral performance and CREB phosphorylation suggests that activation of alpha 7 receptors may play an important role in memory enhancement by glucose. (C) 2012 Elsevier Ltd. All rights reserved.

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