Hippocampal injections of amyloid beta-peptide 1-40 impair subsequent one-trial/day reward learning

The injection of amyloid beta -peptide (A beta) into rat CNS has been repor ted to induce cellular neuropathology. The present study investigated wheth er multiple intrahippocampal injections of A beta 1-40 would impair one-tri al/day reward learning 14 days later. Twenty-four male Sprague-Dawley rats, 3-4 months old, were injected with either A beta 1-40 or distilled water i nto seven hippocampal sites bilaterally. Ten rats received 3 nmol A beta 1- 40 in 2 mul of distilled water per injection site, while 14 rats received d istilled water alone. Following a 9-day recovery period, rats were graduall y food deprived to 82% of their initial body weight. Fourteen days after th e intrahippocampal injection, all rats received an initial training trial a nd three subsequent daily retention trials. Rats receiving A beta 1-40 were significantly impaired on the second retention trial in terms of accuracy (number of unbaited alleys entered) and on the second and third retention t rials in terms of speed (reciprocal of latency to reward). Histological ana lysis showed that A beta 1-40 injections produced significant neuronal loss and gliosis. A beta 1-40 immunoreactivity persisted locally at the injecti on site and in macrophages 2 weeks following the hippocampal injections. Th ese effects appear to be sequence-specific; rats receiving A beta 1-42 with a scrambled peptide sequence did not differ significantly from rats receiv ing distilled water alone in retention of the learning task or degree of hi stological damage. (C) 2001 Academic Press.