The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats

Abstract

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.

In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes

“…Furthermore, it was reported that the effects of the hallucinogen 5-MeO-DMT on locomotor activity and prepulse inhibition of the startle paradigm were elicited by the activation of 5-HT 1A and 5-HT 2 receptors. 20) These findings and our present study suggest that psychoactive drugs have complex interactions in neurotransmitter systems. Given our finding that the activity of the five drugs was almost completely inhibited by methiothepin, it is necessary to investigate the role of receptor subtypes in the in vivo effects of these drugs by means of future animal studies.…”

Psychedelics

“…Although not specific for psychedelics, studies of effects on locomotor and open field behavior are simple to implement and are often the first animal model to study. Krebs-Thomson et al (2006) reported that 5-MeO-DMT decreased locomotor activity, investigatory behavior, and center duration and disrupted prepulse inhibition (PPI) of startle in rats. All of these effects were blocked by pretreatment with the 5-HT 1A antagonist WAY-100635.…”

Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens

“…First, LSD more potently bound to 5-HT 2A receptors compared with all of the tryptamines. Second, LSD was absolutely and in most cases also relatively more potent than all of the tryptamines at the 5-HT 1 receptor, which may moderate the in vivo effects of hallucinogens Krebs-Thomson et al, 2006;Sipes and Geyer, 1994;15 Strassman, 1996). Third, all of the novel tryptamines were full agonists at the 5-HT 2A receptor or presented > 50% activation efficacy, whereas LSD, DMT, and psilocin were partial agonists with < 40% activation efficacy.…”