Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats.
European journal of pharmacology – January 15, 1985
Source: PubMed
Summary
Chronic exposure to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) led to significant tolerance in rats, with the effective dose needed for behavioral effects rising from 1.3 mg/kg to 2.4 mg/kg. The duration of the drug's syndrome effect dropped dramatically from 14.9 minutes to just 1.2 minutes. Notably, this tolerance vanished within four hours after stopping treatment, indicating a rapid recovery process. The findings suggest that the tolerance is linked to reduced binding of the drug to serotonin receptors, rather than changes in brain uptake.
Abstract
Chronic administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 2 mg/kg i.p., every 30 min for 4 h) produced a dramatic tolerance to the behavioral effects of the drug in rats. The ED50 for the syndrome-inducing effects of the drug was increased from 1.3 to 2.4 mg/kg, and the mean duration of the syndrome was decreased from 14.9 to 1.2 min after this treatment. This tolerance effect totally disappeared within 4 h following termination of drug treatment. This effect was not due to changes in the uptake of 5MeODMT into the brain, but rather appears to be due to a decrease in the binding of the drug to serotonin receptors in the central nervous system. These studies are in contrast to previous results which reported no development of tolerance to 5-MeODMT.