COMPENSATORY CHANGES IN THE HIPPOCAMPUS FOLLOWING INTRADENTATE INFUSION OF COLCHICINE

Direct infusion of colchicine into the dentate gyrus of the hippocampu s kills granule cells and elicits behavioral, neurochemical and neuroa natomical changes. Colchicine-treated rats are less sensitive to the b ehavioral effects of cholinergic muscarinic receptor antagonists and m ore sensitive to cholinergic agonists. These behavioral changes are as sociated with time- and dose-dependent alterations in the cholinergic signal transduction mechanism. Carbachol-stimulated turnover of phosph oinositides is increased in the hippocampus of colchicine-treated rats ; similar changes are not observed in the cortex or striatum of colchi cine-treated animals. Intradentate colchicine produces a significant i ncrease in choline- acetyltransferase activity and staining for acetyl cholinesterase activity in the hippocampus, suggesting reactive synapt ogenesis of cholinergic fibers. Other studies have shown that the inte grity of the septohippocampal pathway is necessary for these colchicin e-induced compensatory changes to occur. It is suggested that the mech anism for these neurochemical changes in colchicine-treated animals ma y be occurring via alterations in negative feedback control of recepto r-G-protein-mediated phosphoinositide hydrolysis. (C) 1994 Intox Press , Inc.