The serotonin 5-hydroxytryptamine 2A (5-HT2A) receptor has been related to hallucinogenic effects. Tolerance to hallucinogens has been observed in humans and laboratory animals, but the understanding of tolerance and cross-tolerance between structural classes of hallucinogens is limited. Here, the authors used the head twitch response (HTR) in mice to assess the development of tolerance and cross-tolerance with two phenethylamine-derived drugs (DOI [2,5-dimethoxy-4-iodoamphetamine] and 2C-T-7 [2,5-dimethoxy-4-propylthiophenethylamine]) and two tryptamine-derived drugs (DPT [N,N-dipropyltryptamine] and DIPT [N,N-diisopropyltryptamine]) with agonist affinity for 5-HT2A receptors. Tolerance developed to HTR elicited by daily administration of DOI or 2C-T- 7, but not to HTR elicited by DPT or DIPT. In addition, a cross-tolerance was evident when DOI-tolerant mice were tested with the other compounds. These studies suggest that the use of phenethylamine-derived hallucinogens may be limited not only by their hallucinogenic effects, but also by the rapid development of tolerance.
See article at J Pharmacol Exp Ther 2014, 351:485–491.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics