A Morphologic Study of the Effects of LSD on Neurons in Cultures of Cerebellum

Lysergic acid diethylamide (LSD) primarily targets the lysosomal system within neurons. In organotypic cultures of mouse cerebellum exposed to LSD for up to 53 hours, coarse granules developed in the cytoplasm of mature neurons and outgrowth cells. Electron microscopy revealed these granules were dense bodies, specifically lysosomes, which became heterogeneous dense bodies over time. Synaptic junctions and other organelles remained unchanged. The findings suggest LSD enters cells and interacts with lysosomes, potentially altering neuronal excitability through increased endocytosis or shifts in internal metabolism, which may underlie behavioral changes.

Study at a glance

Abstract

This study was undertaken to examine the possible cytologic action of LSD-25, lysergic acid diethylamide, on nervous tissue. Organotypic cultures of mouse cerebellum were exposed to LSD in their nutrient medium for periods up to 53 hours. Light-microscopically, at a dose of 10-3 M, coarse granules developed in the cytoplasm of mature neurons and in the cytoplasm of cells in the outgrowth region. Electron microscopy of these LSD-induced changes in the neurons revealed that the major qualitative change was the development of dense bodies, i.e. lysosomes. After several hours of exposure, these became heterogeneous dense bodies, HDBs, complex and varied in composition. The synaptic junction and other cell organelles were not altered morphologically. It was concluded that the cytologic site of action of LSD is the lysosomal system. Since it is known that LSD enters the cell, the possible site of interaction between the drug and the lysosomal system of the cell was considered. Two hypotheses were advanced in an attempt to correlate the effects on the lysosomal system of neurons and the known alterations in behaviour produced in man and animals by LSD: (i) an increase of endocytosis, and/or (ii) a shift of the internal metabolism of the cell. Either situation could result in an alteration of the excitability characteristics of a neuron.