Pre- and postsynaptic localization of 3H-imipramine binding sites: action of 5-7 dihydroxytryptamine and triton X-100 on subcellular fractions of rat brain.

In rats injected intraventricularly with 5-7 dihydroxytryptamine there was a considerable reduction of 5-hydroxytryptamine and 5-hydroxyindol acetic acid content in cerebral cortex and hippocampus. After cell fractionation of these structures, a 37% reduction of 3H-imipramine binding was observed in the crude mitochondrial fraction of the treated rats, that contains the synaptosomes. In purified synaptosomal membranes the reduction was about 20%. Dissolution of the presynaptic membrane with 0.1 and 0.2% Triton X-100 on the treated membranes further reduced 3H-imipramine binding respectively by 25% and 40%, values similar to those obtained on control synaptosomal membranes. These findings were further substantiated using saturation experiments for the high affinity site of 3H-imipramine. The results obtained are discussed in relation to the possible mechanism of action of antidepressant drugs at the synaptic region, and the possible postsynaptic effect is emphasized.