Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats.
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.
D000818:Animals; D001921:Brain / Q000187:drug effects; D004361:Drug Tolerance; D008297:Male; D008732:Methoxydimethyltryptamines / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism
D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D012701:Serotonin