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: Article

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

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: Article

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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