Neurochemical and behavioral effects of N-ethyl-acetylcholine aziridinium chloride in mice.

N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EAA) were shown to be inhibitors of high affinity choline uptake in vitro (IC50 = 0.4 microM and 1.5 microM, respectively), and intraventricular administration showed that EAA was more selective in its inhibition of hippocampal choline uptake in vivo. EAA significantly reduced the activity of choline acetyltransferase in the hippocampus 3 to 28 days following intraventricular infusion, but not in the striatum or parahippocampal cortex. Neither muscarinic receptor binding nor glutamic acid decarboxylase activity were affected in any of the three brain regions. EAA (12 or 16 nanomoles, intraventricular) significantly impaired memory performance of mice in a radial arm maze when tested two weeks after treatment. A subgroup analysis implicated long-term reference memory as the mechanism disrupted.