Pharmacological and behavioral components of tolerance to LSD and mescaline in rats

Rats trained to press a lever for water on a fixed-ratio schedule (FR-10) developed tolerance to the disruptive effects of LSD and mescaline when the drugs were given daily before testing. Rats that received the same daily doses after each session did not become tolerant when later tested before a session. This suggests that tolerance to the performance-disrupting effects of these hallucinogens depends on the opportunity to practice the behavior while under the drug's influence, indicating a behavioral compensatory mechanism rather than a purely pharmacological one.

Study at a glance

Abstract

A fixed-ratio schedule of water reinforcement (FR-10) was used to examine the relative contributions of pharmacological and behavioral mechanisms in the development of tolerance to the disruptive effects of LSD and mescaline in the rat. Rats treated daily with LSD or mescaline before operant testing developed tolerance to the impairement of responding, while rats treated daily after each session did not display tolerance when the drugs were administered before testing. These results indicate that behavioral compensatory mechanisms may be involved in the development of tolerance to the disruptive effects of LSD and mescaline on fixed-ratio (FR-10) performance.