Studies on the subsynaptosomal distribution of psychotropic drugs in rat cerebral cortex

After administration of H3-imipramine, H3-dimetacrine and S35-chlorpromazine by the direct lateral intraventricular injection, synaptosomes-rich fraction (F-B) was isolated from rat cerebral cortex by differential and 3-stepwise density gradient centrifugation. The isolated F-B fraction was treated by hyposmotic-lysis followed by freezing and thawing once or 15 times and, furthermore, fractionated into the subsynaptosomal distribution of these drugs showed the same distribution patterns, i.e., the larger portion of radioactivity was recovered in the synaptic ghost membranes-rich fractions. On the other hand, synaptic vesicles-rich fractions contained less radioactivity. On the disrupting process of F-B fraction, when the F-B fraction was treated by hyposmotic-lysis followed by freezing and thawing 15 times, only pellet (FD-6) fraction was obtained as compared with freezing and thawing once (4 interphase layers were obtained). Morphological examination revealed that the synaptic ghost membranes were located in the FD-6 fraction, but morphological damages were not observed. Under these conditions, H3-imipramine showed a 74.1% of release from the synaptosomes, while release with H3-dimetacrine and S35-chlorpromazine was 3.9 and 11.3%, respectively.