Biochemical and behavioral effects of intrahippocampal AF64A in rats

AF64A (ethylcholine aziridinium, 1 nmole) injected into the dorsal hippocampus of the rat decreased choline acetyltransferase activity there by 20% without greatly affecting adjacent areas. The decrease was maximal by 3 days, and persisted for at least 3 weeks. The acetylcholine concentration at the injection site was decreased by 25-30% from 3 days to 4 weeks. Rats were trained on a continuous reinforcement (CRF) food-reinforced lever press schedule and then injected bilaterally in the dorsal and ventral hippocampus. Subsequent switching to a daily CRF-extinction schedule resulted in increased responding during extinction compared to controls which persisted for at least 13 session. However, injection after switching schedules increased it for only 2 sessions. This indicates that the persistently increased extinction responding is due mainly to impaired learned habituation to a new schedule. Most of the extinction effect of the intrahippocampal AF64A was due to its injection at the dorsal site. Separate rats which were trained on the 8-arm radial maze task (a test of short-term spatial working memory) and injected as above only showed marginally impaired task performance even at higher doses. We conclude that even relatively minor, localized, cholinergic deficits confined to the hippocampus can produce significant learning and memory impairments in situations where intermediate or long term memory formation is required.