Amyloid-β production in aged guinea pigs: atropine-induced enhancement is reversed by naloxone

Advanced age, cholinergic deficit, and elevated brain levels of enkephalin are associated with sporadic Alzheimer's disease. The influence of these factors on production of amyloidogenic peptides (Aβ) is uncertain. In the present experiments, the levels of 40/42 amino acid-residue Aβ were measured in the brain cortex of guinea pigs aged 15-16 weeks (young) and 25-26 months (aged). As was found, injections of atropine (21 days, 5 mg/kg/day) increase Aβ levels in aged but not young animals. This atropine-induced effect was antagonized by simultaneous injections of naloxone (3 mg/kg/day) whereas naloxone alone failed to affect Aβ accumulation. These results are discussed in the light of a possible “acetylcholine - Aβ” feedback loop and an influence of enkephalin on the loop function.