LSD as an agonist of dopamine receptors in the striatum


THE mechanism of the hallucinogenic action of (+)-lysergic acid diethylamide (LSD) is still obscure. Its molecular structure (containing both an indole and a phenylethylamine moiety) suggests the possibility of an interaction with brain monoamines. The earliest hypothesis postulated an antagonistic action of LSD at 5-hydroxytryptamine (5-HT) receptors in the brain1,2. More recent data rather tend to support the view that the hallucinogen mimics at least some of the effects of endogenous cerebral 5-HT3–5. Inhibition of the release of 5-HT is another suggested mechanism of action6. An interaction of LSD with dopaminergic transmission has so far not been demonstrated, although the marked attenuation of LSD-induced symptoms by chlorpromazine and other antipsychotic drugs7–9 may suggest this. Using a modification of the rotational model proposed by Ungerstedt10 we found that LSD acted as a potent agonist at dopamine receptors in the striatum.

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PIERI, L., PIERI, M. & HAEFELY, W. LSD as an agonist of dopamine receptors in the striatum. Nature 252, 586–588 (1974).

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