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

Jan Mulder, Tibor Harkany, Katalin Czollner, Thomas I F H Cremers, Jan N. Keijser, C. Nyakas, Paul G M Luiten

Research output: Contribution to journalArticle

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/1 μl) 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.

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

Fingerprint

Galantamine
N-Methylaspartate
Acetylcholinesterase
Spatial Behavior
Cholinergic Neurons
Choline O-Acetyltransferase
Cholinesterase Inhibitors
Nicotinic Receptors
Cognition
Cholinergic Agents
Acetylcholine
Hippocampus
Alzheimer Disease
Clinical Trials
Therapeutics

Keywords

  • Acetylcholinesterase inhibitor
  • Cholinergic system
  • Excitotoxicity
  • Rat
  • Septo-hippocampal projection
  • Spatial memory

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Mulder, J., Harkany, T., Czollner, K., Cremers, T. I. F. H., Keijser, J. N., Nyakas, C., & Luiten, P. G. M. (2005). Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to the rat medial septum. Behavioural Brain Research, 163(1), 33-41. https://doi.org/10.1016/j.bbr.2005.04.019

Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to the rat medial septum. / Mulder, Jan; Harkany, Tibor; Czollner, Katalin; Cremers, Thomas I F H; Keijser, Jan N.; Nyakas, C.; Luiten, Paul G M.

In: Behavioural Brain Research, Vol. 163, No. 1, 30.08.2005, p. 33-41.

Research output: Contribution to journalArticle

Mulder, Jan ; Harkany, Tibor ; Czollner, Katalin ; Cremers, Thomas I F H ; Keijser, Jan N. ; Nyakas, C. ; Luiten, Paul G M. / Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to the rat medial septum. In: Behavioural Brain Research. 2005 ; Vol. 163, No. 1. pp. 33-41.
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