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Legitimate and illegitimate use of lysergic acid diethylanide (LSD) increased dramatically in the 1960 1 s. Since then, a number of studies have shown that LSD induces -psychotic symptoms in the user, suggesting a possible correlation between exposure to LSD and certain psychoses. This hypothesis is supported by repeated observations that LSD inhibits 5-HT systems in the brain and that central 5-HT systems may be implicated in certain psychoses. The present study was designed to test the hypothesis that chronic administration of LSD to rats has an observable effect on 5-HT neuronal functioning in the brain. Rats were exposed to varying doses of LSD, and sacrificed 1 or 14 days after the last dose. Alteration in the 5-HT system was estimated by measurement of turnover of 5-HT, synaptosomal uptake of (3H)5-HT, and the extent of (3H)5-HT and (3H)spiroperidol binding. The results do not support the hypothesis. Chronic LSD administration had no effect on 5-HT turnover, uptake, or receptor binding. In light of these results, the possibility exists that LSD induces a psychotic effect in humans by other mechanisms. The possibility also exists that the effect in humans is not paralleled in rats.

THE EFFECT OF CHRONICALLY ADMINISTERED LSD ON THE SEROTONERGIC NERVOUS SYSTEM OF THE RAT