Nature 222, 567 - 569 (10 May 1969); doi:10.1038/222567a0

Comparison of Effects of LSD and Amphetamine on Midbrain Raphe Units

WARREN E. FOOTE, MICHAEL H. SHEARD & GEORGE K. AGHAJANIAN

Department of Psychiatry, Yale University School of Medicine and The Connecticut Mental Health Center, New Haven, Connecticut 06508.

D-Lysergic acid diethylamide (LSD) given pareriterally produces a reversible cessation of the spontaneous activity of neuronal units in the midbrain raphe nuclei of the rat¹. Threshold doses of LSD required to produce this effect are extremely small in relation to those typically used in rats (10–20 g/kg, intravenously). Substances the behavioural effects of which are similar to those of LSD (for example, N,N-dimethyltryptamine and mescaline) also inhibit raphe units, although none is as potent as LSD². A variety of other types of drugs (for example, atropine, phencyclidine, chlorpromazine) do not affect the activity of raphe units². The inhibitory effect of LSD is specific for units in the dorsal and median raphe nuclei; in other mid-brain areas (for example, reticular formation), the drug either has no effect or accelerates unit activity¹. According to the fluorescence histochemical method the midbrain raphe nuclei are comprised of serotonin-containing neurones³. Axons of the raphe neurones supply the principal serotonin input to the forebrain⁴. Large doses of LSD induce a prolonged inhibition of the serotonin-containing neurones¹; this inhibition may account for the reduced metabolism of brain serotonin observed after injections of LSD^5–8.

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