Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to the rat medial septum

J. Mulder, T. Harkany, K. Czollner, T.I.F.H. Cremers, J. Keijser, C. Nyakas, P.G.M. Luiten

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23 Citations (Scopus)

Abstract

Clinical trials show beneficial effects of acetylcholinesterase (AChE) inhibitors, including galantamine, on cognitive functions in patients with mild to moderate Alzheimer's disease. Galantamine shows a dual action profile by also acting as an allosteric modulator of nicotinic acetylcholine receptors. Nevertheless, its in vivo mechanism of action is only partly understood. Here, we first established a novel lesion model provoking significant functional impairment of the septo-hippocampal projection system without triggering massive neuronal death in the rat medial septum. Next, we studied whether galantamine, administered in doses of 1 and 3 mg/kg post-lesion, promotes functional recovery of spatial navigation behaviors, and affects the output of septal cholinergic projections. Infusion of N-methyl-D-aspartate (NMDA; 30 nmol/l mu l) in the medial septum resulted in spatial learning deficits associated with significant shrinkage of cholinergic neurons and reduced AChE activity in the hippocampus at 7 days post-lesion. Galantamine treatment alone significantly increased the hippocampal acetylcholine concentration and attenuated the NMDA-induced spatial learning impairment. Galantamine post-treatment also affected NMDA-induced changes in AChE and choline-acetyltransferase activities. In conclusion, our data show that galantamine attenuates experimentally-induced cognitive impairments underscored by mild neuronal damage. (C) 2005 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)33-41
Number of pages9
JournalBehavioral Brain Research
Volume163
Issue number1
DOIs
Publication statusPublished - 30-Aug-2005

Keywords

  • acetylcholinesterase inhibitor
  • cholinergic system
  • excitotoxicity
  • rat
  • septo-hippocampal projection
  • spatial memory
  • MILD COGNITIVE IMPAIRMENT
  • ALZHEIMERS-DISEASE
  • NUCLEUS BASALIS
  • CHOLINE-ACETYLTRANSFERASE
  • DIAGONAL BAND
  • SELECTIVE IMMUNOLESIONS
  • ACETYLCHOLINE-RELEASE
  • PROJECTION PATTERNS
  • NICOTINIC RECEPTORS
  • IN-VIVO

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