Passive avoidance deficits in mice following ethylcholine aziridinium chloride treatment.

High-affinity choline uptake (HACU) appears to be the rate-limiting step in the synthesis of the neurotransmitter acetylcholine. The present experiment was designed to examine the effects of irreversible inhibition of HACU by ethylcholine aziridinium chloride (ECA) on passive avoidance retention in mice. Animals were injected intracerebroventricularly, and one-trial passive avoidance retention evaluated 21 days later. A significant retention deficit was observed in ECA-treated animals upon retest 24 hours after training. ECA-induced changes in retention were accompanied by significant reductions in choline acetyltransferase (CAT) activity in only two of seven brain regions tested, hippocampus (48% of control) and cerebellum (76% of control). The results support the involvement of hippocampal cholinergic activity in mediation of passive avoidance learning.