Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice.
Jerrold C Winter, D J Amorosi, Kenner C Rice, Kejun Cheng, Ai-Ming Yu
Pharmacology, biochemistry, and behavior September 1, 2011 DOI: 10.1016/j.pbb.2011.05.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Wild-type and Tg-CYP2D6 mice |
| Interventions | 5-MeO-DMT bufotenine acetylbufotenine harmaline |
| Topics | 5-MeO-DMT DMT |
| Keywords | Drug interaction Synergism Potentiation Enhancement Augmentation Combination effects Pharmacological interaction Drug synergy Psychoactive substances Psychedelics Hallucinogens Entheogens Psychotropic drugs Mind-altering substances Consciousness-altering compounds Animal models Preclinical research Rodent studies In vivo studies Experimental animals Laboratory animals Drug discovery research Mouse models Neuropharmacology Pharmacodynamics Pharmacokinetics Drug action Biochemical pharmacology Drug metabolism |
| Citations | 10 |
| Key points | Harmaline enhanced the stimulus effects of 5-MeO-DMT in both wild-type and Tg-CYP2D6 mice, and harmaline alone produced 5-MeO-DMT-appropriate responding in Tg-CYP2D6 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.