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Main Title Comparison of Intracranial Infusions of Colchicine and Ibotenic Acid as Models of Neurodegeneration in the Basal Forebrain. Research Report.
Author Shaughnessy, L. W. ; Barone, S. ; Mundy, W. R. ; Herr, D. W. ; Tilson, H. A. ;
CORP Author North Carolina Univ. at Chapel Hill. Curriculum in Neurobiology. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC. Neurotoxicology Div.
Publisher cFeb 94
Year Published 1994
Report Number EPA-68-D2-5600; EPA/600/J-94/318;
Stock Number PB94-197183
Additional Subjects Colchicine ; Toxicology ; Prosencephalon ; Cognition disorders ; Ibotenic acid ; Comparison ; Choline acetyltransferase ; Immunohistochemistry ; Catecholamines ; Animal behavior ; Reprints ;
Library Call Number Additional Info Location Last
NTIS  PB94-197183 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 14p
Colchicine and ibotenic acid were compared for their ability to produce neurodegeneration and cognitive deficit after bilateral infusions into the nucleus basalis magnocellularis of male Long-Evans rats. Four weeks post-lesion, there was no difference in locomotor activity following infusion of either neurotoxicant or vehicle. In a passive avoidance task, both treated groups had significantly shorter step-through latencies compared with vehicle. Five weeks post-lesion, rats were killed for neurochemistry or histochemistry. Choline acetyltransferase (ChAT) activity in both the frontal and parietal cortex was significantly decreased (25-35%) in the colchicine- and ibotenic acid-infused rats when compared to control. There was no effect of either neurotoxicant on ChAT activity in the hippocampus or striatum. Both neurotoxicants produced damage in the general area of the ventromedial pallidum, although ibotenic acid infusion consistently produced a large area of damage as assessed in Nissl-stained sections. Analysis of the number of ChAT-immunoreactive cells in the nucleus basalis magnocellularis (NBM) showed an average 60% cell loss following colchicine infusion and a 75% cell loss after ibotenic acid infusion. Area of glutamic acid decarboxylase (GAD) staining was significantly decreased in several regions surrounding the NBM for ibotenic acid (51% average decrease), and showed non-significant decreases (28%) following colchicine infusion. Colchicine infusion decreased dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum; ibotenic acid had no effect on brain catechol or indoleamine levels. The results indicate that although similar cholinergic hypofunction and behavioral deficits were achieved, several non-cholinergic differences between the neurotoxicants were detected. (Copyright (c) 1994 Elsevier Sciences B.V.)