Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents.
Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases.
Tilson
H A
HA
Laboratory of Behavioral and Neurological Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
McLamb
R L
RL
Shaw
S
S
Rogers
B C
BC
Pediaditakis
P
P
Cook
L
L
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D001679:Biogenic Amines / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D013388:Succinimides / Q000494:pharmacology
D001679:Biogenic Amines; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D013388:Succinimides; C001886:2-ethyl-8-methyl-2,8-diazaspiro(4,5)decane-1,3-dione; D009538:Nicotine; D010830:Physostigmine; D003078:Colchicine