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
Psychopharmacology September 1, 2005 DOI: 10.1007/s00213-005-0009-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice and rats |
| Interventions | 2C-T-7 R(-)-DOM M100907 |
| Dose | 0.01 mg/kg M100907, 0.05 mg/kg M100907 |
| Duration | 10 min for head twitch quantification |
| Topics | Serotonin |
| Keywords | Hallucinogens Psychedelics Psychoactive compounds 2c-t-7 LSD-Like Effects Psychotomimetics Perceptual effects Serotonin receptor Receptor antagonism Receptor engagement Drug target Mechanism of action Pharmacodynamics Drug action Receptor interaction Neuropharmacology Preclinical research Animal models Drug effects Behavioral studies |
| Citations | 72 |
| Key points | 2C-T-7 acts as a 5-HT2A agonist in rodent models, and its behavioral effects are blocked by a selective 5-HT2A antagonist. |
Abstract
Few studies have examined the effects of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in vivo. 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. 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. 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. 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.