Beta-amyloid(Phe(SO3H)24)25-35 in rat nucleus basalis induces behavioral dysfunctions, impairs learning and memory and disrupts cortical cholinergic innervation

Behav Brain Res. 1998 Feb;90(2):133-45. doi: 10.1016/s0166-4328(97)00091-0.


Long-term behavioral effects, changes in learning and memory functions and aberrations of cholinergic fibers projecting to the parietal cortex were investigated after bilateral injections of beta-amyloid(Phe(SO3H)24)25-35 peptide in rat nucleus basalis magnocellularis (nbm). The beta-amyloid peptide used in these experiments contained the original beta-amyloid 25-35 sequence which was coupled to a phenylalanine-sulphonate group at position 24. This additional residue serves as a protective cap on the molecule without influencing its neurotoxic properties and results in water-solubility, stability and low rates of peptide metabolism. In this paper, home cage, locomotor and open-field activities, passive shock-avoidance and 'Morris' water maze learning abilities were assessed throughout a 35-day survival period. Subsequently, acetylcholinesterase (AChE) histochemistry was used to visualize alterations of parietal cortical cholinergic innervation. In response to the neurotoxic action of beta-amyloid(Phe(SO3H)24)25-35, a progressive hyperactivity developed in the rats in their home cages which were maintained throughout the 5-week post-injection period. This was accompanied by a significant hypoactivity in the novel environment of a locomotor arena. Beta-amyloid(Phe(SO3H)24)25-35-treated animals showed greatly impaired cortical memory functions in the step-through passive shock-avoidance paradigm, while spatial learning processes remained unaffected. Moreover, beta-amyloid(Phe(SO3H)24)25-35 injections in the nucleus basalis suppressed explorative behavior in rats and inhibited conditioned stress responses 28 days after surgery. Reductions of cortical cholinergic (AChE-positive) projections provided anatomical substrate for the behavioral changes. This indicated extensive, long-lasting neurodegenerative processes as a result of beta-amyloid(Phe(SO3H)24)25-35 infusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / chemical synthesis
  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology*
  • Electroshock
  • Histocytochemistry
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / psychology
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced*
  • Memory Disorders / psychology
  • Motor Activity / drug effects
  • Neuropeptides / pharmacology
  • Neurotoxins / chemical synthesis
  • Neurotoxins / pharmacology*
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiology*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Amyloid beta-Peptides
  • Neuropeptides
  • Neurotoxins
  • Peptide Fragments
  • beta-amyloid(phenyl(SO3H)24)25-35 peptide
  • Acetylcholinesterase