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

J. C. Winter, D. J. Amorosi, Kenner C. Rice, Kejun Cheng, Aiming Yu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)311-315
Number of pages5
JournalPharmacology Biochemistry and Behavior
Volume99
Issue number3
DOIs
StatePublished - Sep 2011
Externally publishedYes

Fingerprint

Bufotenin
Methoxydimethyltryptamines
Cytochrome P-450 CYP2D6
Harmaline
Serum
Lipids

Keywords

  • 5-methoxy-N,N-dimethyltryptamine
  • CYP2D6
  • Drug interaction
  • Drug-induced stimulus control
  • Harmaline
  • Humanized mice

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice. / Winter, J. C.; Amorosi, D. J.; Rice, Kenner C.; Cheng, Kejun; Yu, Aiming.

In: Pharmacology Biochemistry and Behavior, Vol. 99, No. 3, 09.2011, p. 311-315.

Research output: Contribution to journalArticle

Winter, J. C. ; Amorosi, D. J. ; Rice, Kenner C. ; Cheng, Kejun ; Yu, Aiming. / Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice. In: Pharmacology Biochemistry and Behavior. 2011 ; Vol. 99, No. 3. pp. 311-315.
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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.",
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