Neurotoxic lesions of the nucleus basalis induced by colchicine: effects on spatial navigation in the water maze.
Neuronal loss in the nucleus basalis magnocellularis (NBM) has been consistently associated with learning and memory impairments. Previous studies have used excitotoxicants such as kainic acid or ibotenic acid to examine the behavioral consequences of NBM lesions. In the present study, rats were given bilateral injections of the neurotoxicant colchicine (1.0 micrograms/site) into the NBM and examined for changes in learning and memory. Unlike excitotoxicants, which can produce extensive subcortical damage, colchicine produced a lesion limited to the site of injection. Histological studies demonstrated that colchicine decreased the number of choline acetyltransferase (ChAT)-positive cells in the NBM, and resulted in a marked loss of cortical acetylcholinesterase staining. Separate neurochemical analysis showed that colchicine lesions decreased ChAT activity in the neocortex but not the hippocampus or caudate nucleus. Similar to previous studies, rats with NBM lesions showed a large deficit in a passive avoidance task. Lesions of the NBM impaired acquisition of a reference memory task in the Morris water maze. However, the deficit was transient and with continued training lesioned rats performed as well as controls. In a reversal test in the water maze the learning deficit reappeared. These data suggest that colchicine may be useful in producing lesions of the NBM, which primarily affects the rate of acquisition of a spatial reference memory task.
Mundy
W R
WR
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
Barone
S
S
Tilson
H A
HA
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism / Q000502:physiology*; D003078:Colchicine; D008297:Male; D008568:Memory / Q000502:physiology*; D009498:Neurotoxins; D051381:Rats; D011916:Rats, Inbred F344; D013037:Spatial Behavior
D009498:Neurotoxins; D002795:Choline O-Acetyltransferase; D003078:Colchicine