Autoradiographic Studies on the Distribution of Psychoactive Drugs in the Rat Brain

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Abstract
The distribution pattern of the 14-C labeled neuroleptic spirocompound FR 33 has been studied in 62regions of the rat brain, 1, 30 and 60 minutes after injection, analysing serial sections by autoradiography. The degree of blackening of the autoradiograms was evaluated photometrically. In all structures studied, the radioactivity was highest 1 minute after injection and lowest 60 minutes after injection, the 30-minute values lying in between. Activity decreased more rapidly in the structures of the grey matter (with their high initial values) than in the white matter (with its low initial value). The highest activity was constantly found in the cortex. Sixty minutes after injection, low activity was seen in the reticular formation, the hypothalamus and the limbic system (with the exception of the hippocampus). These structures, however, are regarded as the main sites of action of psychoactive drugs. The effects of these drugs cannot therefore be regarded as being caused by accumulation. The nuclei of the extrapyramidal system belonged to the group of structures with the lowest drug uptake. The distribution pattern of FR 33 was compared with the numerical nerve and glial cell density, volume cell density, capillary density, content of oxidative enzymes, incorporation rate of labeled amino acids, and lipid content of various brain regions, as well as with other patterns described in histochemical and chemical studies in the literature. No meaningful correlation was found.

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