Behavioral sensitivity to LSD: Dependency upon the pattern of central 5HT depletion

Two experiments using a fixed ratio schedule of water reinforcement tested whether serotonin-depleting agents alter sensitivity to a low dose of LSD (0.02 mg/kg). Both p-chloroamphetamine (PCA) and 5,7-dihydroxytryptamine (5,7-DHT) reduced whole-brain serotonin, but only 5,7-DHT increased sensitivity to LSD, disrupting bar-press behavior 12 days after administration. PCA did not produce this effect. However, four PCA-treated animals that showed no increased sensitivity did exhibit behavioral disruption to LSD when pretreated with p-chlorophenylalanine. The pattern of serotonin depletion required for LSD sensitivity may be specific.

Study at a glance

Abstract

Two experiments were carried out using a fixed ratio (FR) schedule of water reinforcement to determine the efficacy of two serotonin (5HT) depleting agents (p-chloroamphetamine, 5, 7-dihydroxytryptamine) in altering sensitivity to a low dose of LSD (0.02 MG/KG). The results showed that while both p-chloroamphetamine (PCA) and 5, 7 dihydroxytryptamine (5, 7 DHT) were efficacious in reducing whole brain 5HT, only 5, 7 DHT altered LSD sensitivity such that a 0.02 mg/kg dose of LSD given 12 days after 5, 7 DHT administration disrupted bar press behavior. This was not observed in animals given PCA within similar parameters. Moreover, 4 animals given PCA that did not show increased sensitivity to LSD, did show behavioral disruption to LSD (0.02 mg/kg when they were pretreated with p-chlorophenylalanine, Results are discussed on terms of a possible particular pattern of 5HT depletion that must be achieved before sensitivity to LSD is observed.