Hippocampal Injections of Amyloid β-Peptide 1-40 Impair Subsequent One-Trial/Day Reward Learning

The injection of amyloid β-peptide (Aβ) into rat CNS has been reported to induce cellular neuropathology. The present study investigated whether multiple intrahippocampal injections of Aβ 1-40 would impair one-trial/day reward learning 14 days later. Twenty-four male Sprague-Dawley rats, 3–4 months old, were injected with either Aβ 1-40 or distilled water into seven hippocampal sites bilaterally. Ten rats received 3 nmol Aβ 1-40 in 2 μl of distilled water per injection site, while 14 rats received distilled water alone. Following a 9-day recovery period, rats were gradually food deprived to 82% of their initial body weight. Fourteen days after the intrahippocampal injection, all rats received an initial training trial and three subsequent daily retention trials. Rats receiving Aβ 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 trials in terms of speed (reciprocal of latency to reward). Histological analysis showed that Aβ 1-40 injections produced significant neuronal loss and gliosis. Aβ 1-40 immunoreactivity persisted locally at the injection site and in macrophages 2 weeks following the hippocampal injections. These effects appear to be sequence-specific; rats receiving Aβ 1-42 with a scrambled peptide sequence did not differ significantly from rats receiving distilled water alone in retention of the learning task or degree of histological damage.