STUDIES ON THE SUBSYNAPTOSOMAL DISTRIBUTION OF PSYCHOTROPIC DRUGS IN RAT CEREBRAL CORTEX

Abstract

After administration of 3H-imipramine, 3H-dimetacrine and 35S-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 fractionated into the subsynaptosomal fractions by 5-stepwise density gradient centrifugation. 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. 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, 3H-imipramine showed a 74.1% or release from the synaptosomes, while release with 3H-dimetacrine and 85S-chlorpromazine was 3.9 and 11.3%, respectively.