Psychopharmacology

, Volume 181, Issue 3, pp 496–503 | Cite as

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
Original Investigation

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.

Keywords

2C-T-7 Hallucinogens Phenethylamines Drug discrimination Head twitch response 5-HT2A receptor Mice Rats 

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Copyright information

© Springer 2005

Authors and Affiliations

  • William E. Fantegrossi
    • 1
    • 2
  • Andrew W. Harrington
    • 2
  • Justin R. Eckler
    • 3
  • Sadia Arshad
    • 3
  • Richard A. Rabin
    • 3
  • Jerrold C. Winter
    • 3
  • Andrew Coop
    • 4
  • Kenner C. Rice
    • 5
  • James H. Woods
    • 2
  1. 1.Division of Neuroscience, Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  2. 2.Department of PharmacologyUniversity of Michigan Medical SchoolAnn ArborUSA
  3. 3.Department of Pharmacology, School of Medicine and Biomedical SciencesState University of New York at BuffaloBuffaloUSA
  4. 4.Department of Pharmaceutical SciencesUniversity of Maryland School of PharmacyBaltimoreUSA
  5. 5.Laboratory of Medicinal ChemistryNIDDK, National Institutes of HealthBethesdaUSA

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