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LONG-TERM BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF INTRADENTATE ADMINISTRATION OF COLCHICINE IN RATS
Citation:
Tandon, P., S. Barone, E. Drust, AND H. Tilson. LONG-TERM BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF INTRADENTATE ADMINISTRATION OF COLCHICINE IN RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/127 (NTIS PB91211508), 1991.
Description:
Previous work has shown that the intradentate administration of colchicine produces time-dependent behavioral and neurochemical changes. eficits in learning and memory and alterations In the signal transduction process for the cholinergic muscarinic receptor have been observed up to 12 weeks after colchicine treatment. o study the long-term effects of colchicine administration on cognitive function and the cholinergic system, 6 month-old male, Fischer-344 rats were injected with 2.5 ug of colchicine bilaterally in the dorsal and ventral hippocampus. welve months later the animals were tested for the acquisition of a spatial reference memory task in the Morris water maze for 8 days, with 4 trials of 60 seconds each day. t the completion of the behavioral testing, one half of the rats were used for histochemical studies. he remaining animals were sacrificed, the hippocampus removed and used for the estimation of receptor-stimulated turnover of phosphoinositides (PI). 3H]-Inositol was incorporated into the hippocampal slices, and various receptor agonists (carbachol, norepinephrine, serotonin) used to stimulate PI turnover in the presence of lithium. ignificant deficit in acquisition In the water maze was observed In animals 1 year after colchicine administration. eurochemical studies showed an increase in carbachol-induced PI metabolism in the rat hippocampus 1 year post-lesion with colchicine. owever, in contrast to results obtained 12 weeks after lesioning, no significant changes were observed in norepinephrine or serotonin-induced PI metabolism 1 year after lesioning. irenzepine, a Ml receptor antagonist, produced a greater degree of inhibition (62%) in lesioned animals as compared to the age-matched controls (20%). ncreased staining for acetylcholinesterase was found in the hippocampus of treated rats. his effect is similar to that observed 12 weeks after lesioning. hese data suggest that the effects of colchicine on the cholinergic system are long-lasting and can be observed a year after treatment.