COMPENSATORY ALTERATIONS IN RECEPTOR-STIMULATED PHOSPHOINOSITIDE HYDROLYSIS IN THE HIPPOCAMPUS VARY AS A FUNCTION OF DOSE OF COLCHICINE

The stimulation of inositol phospholipid (PI) hydrolysis by various receptor agonists was measured in the hippocampus of rats 12 weeks after various concentrations (0.5-2.0-mu-g/site) of colchicine were infused into the dentate gyrus. Colchicine produced a dose-related decrease in the average width and length of the granule cell line; the pyramidal cells in CA1 and CA3 regions of the hippocampus were affected only at higher concentrations of colchicine. Compensatory increases in receptor-mediated hydrolysis of phosphoinositides (PI) in hippocampal slices were seen at 100-mu-m carbachol and ibotenic acid in rats receiving 1.5-3.5-mu-g colchicine/site. Compensatory increases in norepinephrine (100-mu-m) and N-methyl-D-aspartate (100-mu-m) stimulated PI were seen at 2.5-3.5 and 3.5-mu-g colchicine/site, respectively. Compensatory increases in PI hydrolysis were not seen in slices from animals receiving 0.5-mu-g colchicine/site. These data support the hypothesis that the signal transduction system in the hippocampus undergoes a compensatory change following experimentally induced destruction of dentate gyrus granule cells. In addition, these changes occur for more than one neurotransmitter and the alterations vary as a function of the size of the lesion.