Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice

Pharmacol Biochem Behav. 2011 Sep;99(3):311-5. doi: 10.1016/j.pbb.2011.05.015. Epub 2011 May 23.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Central Nervous System Stimulants / administration & dosage
  • Cytochrome P-450 CYP2D6 / genetics*
  • Dose-Response Relationship, Drug
  • Harmaline / administration & dosage
  • Humans
  • Male
  • Methoxydimethyltryptamines / biosynthesis
  • Methoxydimethyltryptamines / blood
  • Methoxydimethyltryptamines / pharmacology*
  • Mice
  • Mice, Transgenic
  • Reaction Time / drug effects*
  • Reaction Time / genetics
  • Reaction Time / physiology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Central Nervous System Stimulants
  • Methoxydimethyltryptamines
  • Harmaline
  • Cytochrome P-450 CYP2D6