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

Behav Brain Res. 2005 Aug 30;163(1):33-41. doi: 10.1016/j.bbr.2005.04.019.


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 3mg/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; 30nmol/1microl) 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Choline O-Acetyltransferase / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Fibers / drug effects*
  • Cholinergic Fibers / enzymology
  • Cholinesterase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Galantamine / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Male
  • Maze Learning / drug effects*
  • Maze Learning / physiology
  • Models, Animal
  • N-Methylaspartate
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / enzymology
  • Neural Pathways / drug effects
  • Neural Pathways / enzymology
  • Neurotoxins
  • Nicotinic Antagonists / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / metabolism
  • Septal Nuclei / drug effects*
  • Septal Nuclei / enzymology
  • Space Perception / drug effects


  • Cholinesterase Inhibitors
  • Neurotoxins
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Galantamine
  • N-Methylaspartate
  • Choline O-Acetyltransferase
  • Acetylcholinesterase