The Roles of 5-HT1A and 5-HT2 Receptors in the Effects of 5-MeO-DMT on Locomotor Activity and Prepulse Inhibition in Rats

Psychopharmacology (Berl). 2006 Dec;189(3):319-29. doi: 10.1007/s00213-006-0566-1. Epub 2006 Sep 30.

Abstract

Rationale: The hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is structurally similar to other indoleamine hallucinogens such as LSD. The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm.

Objectives: A series of interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg), the 5-HT(2A) antagonist M100907 (1.0 mg/kg), and the 5-HT(2C) antagonist SER-082 (0.5 mg/kg) were performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) in the BPM and PPI paradigms.

Results: 5-MeO-DMT decreased locomotor activity, investigatory behavior, the time spent in the center of the BPM chamber, and disrupted PPI. All of these effects were antagonized by WAY-100635 pretreatment. M100907 pretreatment failed to attenuate any of these effects, while SER-082 pretreatment only antagonized the PPI disruption produced by 5-MeO-DMT.

Conclusions: While the prevailing view was that the activation of 5-HT(2) receptors is solely responsible for hallucinogenic drug effects, these results support a role for 5-HT(1A) receptors in the effects of the indoleamine hallucinogen 5-MeO-DMT on locomotor activity and PPI in rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Lysergic Acid Diethylamide / pharmacology
  • Male
  • Methoxydimethyltryptamines / pharmacology*
  • Motor Activity / drug effects*
  • Neural Inhibition / drug effects*
  • Neural Inhibition / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Receptor, Serotonin, 5-HT2A / physiology*

Substances

  • Methoxydimethyltryptamines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT1A
  • Lysergic Acid Diethylamide