AF64A disrupts retrieval processes in long-term memory of mice

Intracerebroventricular (i.c.v.) injection of ethylcholine mustard aziridinium ion (AF64A) in mice caused a reversible impairment of retrieval processing in long-term memory. After long retention intervals (1-3 weeks), AF64A-treated mice demonstrated marked impairment of behavioural performance previously acquired in a complex multiple maze task. This behavioural deficit was dose dependently ameliorated by the administration of oxotremorine. In parallel with the behavioural deficit, AF64A selectively decreased acetylcholine (ACh) levels in the hippocampus. These findings suggest that the reversible behavioural deficit induced by AF64A should be regarded as a retrieval failure in long-term memory, and not as a retention failure. This failure was largely associated with dysfunction of the cholinergic neuronal system in the hippocampus.