Reversal of scopolamine-induced spatial and recognition memory deficits in mice by novel multifunctional dimers bis-cognitins.

Abstract

Our previous reports indicated that bis(propyl)-cognitin (B3C) and bis(heptyl)-cognitin (B7C), as novel dimers derived from tacrine, may be potential multifunctional drugs for treating Alzheimer's disease. There is little knowledge on the cognitive function of B3C while B7C appeared to reverse learning and memory impairments. In this study, for the first time, we evaluated the anti-amnesic effects of B3C and B7C on learning and memory deficits induced by scopolamine using both Morris water maze and novel object recognition tasks in mice. Under the same experimental condition, the anti-amnesic effect of tacrine was also compared. Briefly, in both tasks, scopolamine (0.1-0.6 mg/kg, ip) dose-dependently impaired learning and memory functions. B3C (1.5-2.5 μmol/kg), B7C (0.4-0.6 μmol/kg) or tacrine (8-12 μmol/kg), each administered ip, dose-dependently mitigated scopolamine-induced learning and memory impairments in both tasks. Our present results show, for the first time, that B3C and B7C reverse cognitive impairment resulted from scopolamine in both water maze and object recognition tasks; and under the same condition, the relative potency of B3C and B7C to improve cognitive capacity was 5-20 folds over that of tacrine. These novel in vivo findings further demonstrate that both B3C and B7C may potentially be developed as Alzheimer's therapeutic drugs for different severities of neurodegenerations.

• Authors: Ren-wen Han, Rui-san Zhang, Min Chang, Ya-li Peng, Pei Wang, Sheng-quan Hu, Chung-lit Choi, Ming Yin, Rui Wang, Yi-fan Han
• Journal: Brain research (Brain Res) Vol. 1470 Pg. 59-68 (Aug 27 2012) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 22750583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Cholinergic Antagonists
• Cholinesterase Inhibitors
• Tacrine
• Scopolamine

Topics

• Analysis of Variance
• Animals
• Cholinergic Antagonists (toxicity)
• Cholinesterase Inhibitors (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Learning Disabilities (chemically induced, drug therapy)
• Male
• Maze Learning (drug effects)
• Memory Disorders (chemically induced, drug therapy)
• Mice
• Mice, Inbred Strains
• Reaction Time (drug effects)
• Recognition, Psychology (drug effects)
• Retention, Psychology (drug effects)
• Scopolamine (toxicity)
• Tacrine (therapeutic use)