A Quantitative regional analysis of protein synthesis inhibition in the rat brain following localized injection of cycloheximide

Previous work has shown that bilateral injection of as little as 10 μg of cycloheximide (CHX) into the amygdala, but not into the internal capsule, caused a time-dependent disruption of long-term retention of passive avoidance training. Under these conditions, protein synthesis in the entire brain was inhibited by less than 10%. The present study was undertaken to quantify the resulting inhibition of protein synthesis in various brain regions (amygdala, internal capsule, caudate, cortex, hippocampus, thalamus, hypothalamus and the entire half brain). Rats were subcutaneously injected with L-[ 14C-methyl]methionine following unilateral administration of CHX via a cannula implanted in either the amygdala or the internal capsule. Regional inhibition of protein synthesis was determined by analysis of autoradiograms from different brain levels using an image analyzing computer to measure the optical densities of microscopic areas corresponding to discrete neuroanatomical structures. Regional patterns of inhibition were assessed: (a) after injection of different doses of CHX (10 or 20 μg) into the amygdala; (b) after injection of 20 μg of CHX into the amygdala or internal capsule; and (c) at different times (0.5, 3, 6 and 24 h) after injection of 20 μg of CHX into the amygdala. Quantitative results are presented for the temporal and spatial patterns of protein synthesis inhibition caused by CHX injection. Since injection of CHX into the amygdala resulted in a profound inhibition of protein synthesis in both the amygdala and internal capsule while injection into the internal capsule only caused a marked inhibition in the capsule itself, these results provide a possible explanation for our earlier observation that injection of CHX into the a amy3dala produced a retention deficit while injection into the adjacent internal capsule had no effect on memory function. These observations on protein synthesis inhibition support our earlier hypothesis that CHX injected into the amygdala might impair memory by virtue of its action on amygdaloid function rather than as a result of its effect on the brain as a whole.