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Sloviter RS, Drust EG, Damiano BP, Connor JD.
“A Common Mechanism for Lysergic Acid, Indolealkylamine and Phenethylamine Hallucinogens: Serotonergic Mediation of Behavioral Effects in Rats”.
J. Pharmacol. esp. Ther.. 1980;214(2):231-238.
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Abstract
A rat behavioral model that reflects central serotonin (5-HT) receptor activationin vivo was utilized in a study of indole and phenethylamine hallucinogens. Lysergic acid diethylamide (LSD; 1-4 mg/kg i.p.) caused the 5-HT behavioral syndrome (side-to-side headweaving or head tremor, forepaw padding and splayed hindlimbs). Doses of LSD (10 and 100 mcg/kg) which alone were too low to cause the syndrome, shifted the dose-response curve for 5-methoxy-N,N-dimethyltryptamine (a 5-HT receptor agonist) to the left. No antagonist effects of LSD were detected at any dose tested (10 mcg/kg- 4 mg/kg). Bromo-LSD, a nonhallucinogenic congener of LSD that attenuates LSD hallucinations in man, did not cause the 5-HT behavioral syndrome over a wide dose-range (1-100 mg/kg). However, bromo-LSD (1-10 mg/kg) did block the behavioral effects of LSD, i.e. shifted the LSD dose-response curve to the right. Bromo-LSD (1-10 mg/kg) also shifted the 5-methoxy-N,N-dimethyltryptamine dose-response curve to the right, as did the presumed 5-HT receptor antagonists methysergide, metergoline and mianserine. All indole and phenethylamine hallucinogens tested (5-methoxy-N,N-dimethyltryptamine, N,N-dimethyltryptamine, N,N-diethyltryptamine, ibogaine, mescaline, p-methoxyamphetamine and four other methoxy-substituted amphetamines) evoked the same 5-HT behavioral syndrome in rats as did LSD. Studies on the mechanism by which these compounds activated 5-HT receptors revealed that all except p-methoxyamphetamine were direct 5-HT agonists. p-Methoxyamphetamine produced its behavioral effects primarily through release of endogenous 5-HT. The findings support the hypothesis that lysergic acid, indolealkylamine and phenethylamine hallucinogens share a common mechanism of action, i.e. central 5-HT receptor activation.
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