Noradrenaline depletion protects cholinergic neurons in rat hippocampus against AF64A-induced damage.
The role of the noradrenergic system in the cholinotoxicity of ethylcholine aziridinium ion (AF64A) was studied in rats. Male Sprague-Dawley rats were treated with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine; 50 mg/kg i.p.) in the presence of the serotonin uptake inhibitor fluoxetine, 14 days prior to bilateral intracerebroventricular injection of AF64A (2 nmol/lateral ventricle). In rats in which noradrenaline (NA) was depleted by 94%, the loss of acetylcholine (ACh) in hippocampus induced by AF64A was significantly attenuated (p less than 0.02). However, when there was only a partial depletion of NA (50% reduction), the AF64A-induced loss of ACh was a pronounced as in rats with intact noradrenergic function. These findings indicate that the noradrenergic lesion has to be complete before a protective effect is apparent. Moreover, they imply that noradrenergic input is involved in AF64A-induced cholinergic damage in the hippocampus.
Hörtnagl
H
H
Institute of Biochemical Pharmacology, University of Vienna, Austria.
Potter
P E
PE
Kindel
G
G
Hanin
I
I
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001388:Aziridines / Q000633:toxicity*; D001389:Azirines / Q000633:toxicity*; D001596:Benzylamines / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives* / Q000633:toxicity; D002799:Cholinergic Fibers / Q000187:drug effects / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001388:Aziridines; D001389:Azirines; D001596:Benzylamines; D009498:Neurotoxins; C044894:ethylcholine aziridinium; D002794:Choline; C012102:DSP 4; D009638:Norepinephrine