Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in mice and rats

William E. Fantegrossi, Andrew W. Harrington, Justin R. Eckler, Sadia Arshad, Richard A. Rabin, Jerrold C. Winter, Andrew Coop, Kenner C. Rice, James H. Woods

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Rationale: Few studies have examined the effects of 2,5-dimethoxy-4-(n)- propylthiophenethylamine (2C-T-7) in vivo. Objectives: 2C-T-7 was tested in a drug-elicited head twitch assay in mice and in several drug discrimination assays in rats; 2C-T-7 was compared to the phenylisopropylamine hallucinogen R(-)-1-(2,5-dimethoxy-4-methylphenyl)-2aminopropane (DOM) in both assays, with or without pretreatment with the selective 5-HT2A antagonist (+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907). Finally, the affinity of 2C-T-7 for three distinct 5-HT receptors was determined in rat brain. Methods: Drug-elicited head twitches were quantified for 10 min following administration of various doses of either 2C-T-7 or R(-)-DOM, with and without pretreatments of 0.01 mg/kg M100907. In rats trained to discriminate lysergic acid diethylamide (LSD), 2C-T-7 and R(-)-DOM were tested for generalization. In further studies, rats were trained to discriminate 2C-T-7 from saline, then challenged with 0.05 mg/kg M100907. In competition binding studies, the affinity of 2C-T-7 was assessed at 5-HT2A receptors, 5-HT1A receptors, and 5-HT2C receptors. Results: 2C-T-7 and R(-)-DOM induced similar head twitch responses in the mouse that were antagonized by M100907. In the rat, 2C-T-7 produced an intermediate degree of generalization (75%) to the LSD cue and served as a discriminative stimulus; these interoceptive effects were attenuated by M100907. Finally, 2C-T-7 had nanomolar affinity for 5-HT2A and 5-HT2C receptors and lower affinity for 5-HT1A receptors. Conclusions: 2C-T-7 is effective in two rodent models of 5-HT2 agonist activity and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of 2C-T-7 strongly suggests that the 5-HT2A receptor is an important site of action for this compound.

Original languageEnglish (US)
Pages (from-to)496-503
Number of pages8
JournalPsychopharmacology
Volume181
Issue number3
DOIs
StatePublished - Sep 2005

Keywords

  • 2C-T-7
  • 5-HT receptor
  • Drug discrimination
  • Hallucinogens
  • Head twitch response
  • Mice
  • Phenethylamines
  • Rats

ASJC Scopus subject areas

  • Pharmacology

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