The AF64A model of cholinergic hypofunction: an update.
Based on numerous reports in the literature since 1980, one can now conclude that ethylcholine aziridinium (AF64A) is selective for the cholinergic system in vivo, and that the effect is both dose- and site-dependent. Thus, AF64A treatment, under the correct conditions of dose and time will result in selective reductions in levels of ACh, AChE, ChAT, HAChT, and K(+)- and ouabain-stimulated release of ACh. While other neurotransmitters may also be affected in brains of AF64A treated rats, the effect is only transient and is most probably secondary to the initial cholinergic deficit-induced by AF64A, reflecting an adaptive reaction of these neurotransmitter systems, which are normally integrated with cholinergic interconnections, to the cholinergic deficiency induced by AF64A. This paper provides a historical perspective for the development of AF64A as a selective cholinotoxin, and surveys its potential mechanisms of action at the neurochemical and molecular levels. Moreover, the availability of an animal model such as the AF64A-treated rat, in which the cholinergic system has been compromised selectively for an extended period of time, has allowed investigators to study a wide variety of questions that relate to factors controlling cholinergic function in vivo. Several key illustrations are presented at the end of this paper.
Hanin
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I
Loyola University Chicago, Stritch School of Medicine, Department of Pharmacology, Maywood, Illinois 60153, USA.
D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D002796:Choline Deficiency / Q000378:metabolism*; D018680:Cholinergic Antagonists; D004195:Disease Models, Animal; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D009435:Synaptic Transmission / Q000187:drug effects
D001388:Aziridines; D018680:Cholinergic Antagonists; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002794:Choline