Behavioral evidence for the stimulation of CNS serotonin receptors by high doses of LSD.

Systemic administration of lysergic acid diethylamide (LSD) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of increased activation of central serotonin receptors. Utilizing this behavioral measure, a marked supersensitivity to LSD was observed in rats whose serotonin nerve terminals had been selectively destroyed, and a dramatic tolerance to LSD was observed following its repeated administration to normal rats. These data provide direct evidence that LSD can stimulate CNS serotonin receptors to a degree which markedly affects behavior.