Hallucinogen-like actions of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in mice and rats.
BACKGROUND
Few studies have examined the effects of 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) in vivo.


OBJECTIVE
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.
Fantegrossi
William E
WE
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Drive, Atlanta, GA 30322, USA. wfanteg@emory.edu
Harrington
Andrew W
AW
Eckler
Justin R
JR
Arshad
Sadia
S
Rabin
Richard A
RA
Winter
Jerrold C
JC
Coop
Andrew
A
Rice
Kenner C
KC
Woods
James H
JH
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology*; D013287:Illicit Drugs / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects
C487778:2,5-dimethoxy-4-n-propylthiophenethylamine; D006213:Hallucinogens; D013287:Illicit Drugs; D010627:Phenethylamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D044282:Receptor, Serotonin, 5-HT1A; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D008238:Lysergic Acid Diethylamide