Behavioural and histological effects of low concentrations of intraventricular AF64A.
The effects of ethylcholine mustard aziridinium ion (AF64A; 0.3, 1.0 and 3.0 nmol), injected into each lateral ventricle in the rat, were determined in a range of behavioural tests, each involving a learning component. Effects were observed at 1.0 and 3.0 nmol/side and, to a lesser extent, at 0.3 nmol/side. Habituation of locomotor activity was impaired and deficits in learning were obtained using a variety of mazes including the Morris swimming maze. Slight, non-significant impairments occurred in shock reinforced behaviours. Histologically, marginal effects were observed at 0.3 nmol/side, and slight ventricular dilatation with necrosis of the hippocampus, restricted to the site of injection at 1.0 nmol/side; at 3.0 nmol/side more widespread necrosis was apparent. Biochemical efficacy of the lesions in terms of cholinergic changes was confirmed by analysis of acetylcholinesterase (AChE) levels showing decreases in the hippocampus and the cortex; no studies were carried out with respect to other neurotransmitters. Cognitive deficits can therefore be obtained by i.c.v. injection of AF64A at doses which cause significant cholinergic changes with minimal histological disturbances.
Gower
A J
AJ
UCB, Pharmaceutical Sector, Chemin du Foriest, Braine-l'Alleud, Belgium.
Rousseau
D
D
Jamsin
P
P
Gobert
J
J
Hanin
I
I
Wülfert
E
E
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001388:Aziridines / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000033:anatomy & histology*; D002794:Choline / Q000008:administration & dosage / Q000494:pharmacology / Q000031:analogs & derivatives; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013550:Swimming
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; C044894:ethylcholine aziridinium; D002794:Choline