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Effects of intracerebroventricular administration of ethylcholine aziridinium ion on hippocampal cholinergic system, assayed in vivo by a brain dialysis technique, and on spatial memory of rats
Author(s) -
Tajima Toshihisa,
Yoshimine Noboru,
Goto Tsutomu,
Ikari Hiroyuki,
Kuzuya Fumio,
Endo Hidetoshi
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280110
Subject(s) - hippocampal formation , hippocampus , cholinergic , neuroscience , acetylcholine , psychology , cholinergic neuron , cholinergic system , medicine , endocrinology , anesthesia
We attempted to clarify the effect of hippocampal function on the spatial memory of rats by creating a lesion in the hippocampus with ethylcholine aziridinium ion (AF64A). The hippocampus was damaged by injecting AF64A into the lateral ventricles, 3 nmol/3 μl per side. At 1 or 4 weeks after the injection, acetylcholine (ACh) was measured in perfusion samples collected via brain dialysis of the hippocampus of freely moving rats. The release of ACh stimulated by scopolamine was reduced at 1 week but not at 4 weeks post‐injection. A behavioral change on the eight‐arm radial maze test was also observed in the acquisition or retention trials to determine the deficit in spatial memory, whether acquisition or retention. In the acquisition trial, the initial correct response was decreased and the total error count was increased at 1.5 to 2.5 weeks, but not at 3 weeks, after the AF64A injection. However, those indices remained unchanged in the retention trial. These observations suggest that the hippocampus may be required for the acquisition of spatial memory, but that the stored memory, but the stored memory is located outside the hippocampus, the hippocampus is not concerned with the retrieval process, or the retrieval process may be hippocampal but not cholinergic. The hippocampal cholinergic system would be concerned with the acquisition of spatial memory. Thus, AF64A‐treated rats may serve a model for hippocampal cholinergic dysfunction and the recovery from hippocampal cholinergic damage. © 1993 Wiley‐Liss, Inc.