Colchicine-induced alterations in receptor-stimulated phosphoinositide hydrolysis in the rat hippocampus

Intradentate administration of colchicine has been reported to affect the cholinergic muscarinic system in the hippocampus, causing a reduction in quinclidinylbenzilate binding sites and an increase in choline acetyltransferase activity. Since the cholinergic muscarinic system is coupled to the formation of inositolphosphates in the brain, the effect of intradentate administration of colchicine on the agonist-induced turnover of inositollipid was studied in rats. The animals were sacrificed 12 weeks after injection, and the hippocampi removed and sliced. [3H]Inositol was incorporated into slices in the presence of lithium, and carbachol, a cholinergic muscarinic receptor agonist, was used to study the stimulated turnover of inositollipids. Hippocampal slices taken from colchicine-treated rats showed an increased carbachol-stimulated accumulation of inositolmonophosphate. Thus, intradentate colchicine appears to alter the signal transduction process for the muscarinic cholinergic receptor in the hippocampus, a change that may be associated with compensatory processes following damage to the hippocampus.