title: Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice.
abstract: In previous studies we have observed that, in comparison with wild type mice, Tg-CYP2D6 mice have increased serum levels of bufotenine [5-hydroxy-N,N-dimethyltryptamine] following the administration of 5-MeO-DMT. Furthermore, following the injection of 5-MeO-DMT, harmaline was observed to increase serum levels of bufotenine and 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice. In the present investigation, 5-MeO-DMT-induced stimulus control was established in wild-type and Tg-CYP2D6 mice. The two groups did not differ in their rate of acquisition of stimulus control. When tested with bufotenine, no 5-MeO-DMT-appropriate responding was observed. In contrast, the more lipid soluble analog of bufotenine, acetylbufotenine, was followed by an intermediate level of responding. The combination of harmaline with 5-MeO-DMT yielded a statistically significant increase in 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice; a comparable increase occurred in wild-type mice. In addition, it was noted that harmaline alone was followed by a significant degree of 5-MeO-DMT-appropriate responding in Tg-CYP2D6 mice. It is concluded that wild-type and Tg-CYPD2D6 mice do not differ in terms of acquisition of stimulus control by 5-MeO-DMT or in their response to bufotenine and acetylbufotenine. In both groups of mice, harmaline was found to enhance the stimulus effects of 5-MeO-DMT.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter@buffalo.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Winter
authors.forename: D J
authors.initials: DJ
authors.lastname: Amorosi
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: Kejun
authors.initials: K
authors.lastname: Cheng
authors.forename: Ai-Ming
authors.initials: AM
authors.lastname: Yu
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D006246:Harmaline / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008732:Methoxydimethyltryptamines / Q000096:biosynthesis / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D011930:Reaction Time / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D008732:Methoxydimethyltryptamines; D006246:Harmaline; D019389:Cytochrome P-450 CYP2D6