Differentiation between the stimulus effects of l-5-hydroxytryptophan and LSD.

The stimulus properties of the serotonin precursor 1-5-hydroxytryptophan (5-HTP) and the hallucinogen d-lysergic acid diethylamide (LSD) were compared in a two-lever, water-reinforced drug discrimination task. 5-HTP (in combination with the peripheral decarboxylase inhibitor Ro 4-4602) elicited no more than 50% drug-lever responding in rats trained to discriminate LSD (0.08 mg/kg) from saline while LSD substituted completely in animals trained to discriminate 5-HTP (50 mg/kg) from saline. Combination tests indicated that, while the 5-HTP cue was unaffected by pretreatment with various serotonin antagonists, the substitution of LSD for 5-HTP was abolished by the putative serotonin-2 antagonist ketanserin. It was concluded that LSD mimics 5-HTP by stimulating a subset of serotonin receptors activated by 5-HTP which are sensitive to ketanserin (serotonin-2?).