Skip to content

Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat

Mark D. Tricklebank, Christian Forler, Derek N. Middlemiss, John R. Fozard

European Journal of Pharmacology October 1, 1985 DOI: 10.1016/0014-2999(85)90467-4 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Intact rats and rats depleted of monoamines with reserpine
Interventions 5-methoxy-N N-dimethyltryptamine (5-MeODMT) ketanserin haloperidol pindolol spiperone betaxolol ICI 118.551
Topics Serotonin 5-MeO-DMT DMT
Keywords Ketanserin Pindolol Agonist Methysergide Endocrinology Quipazine 5-HT Receptor Dopamine receptor Monoamine neurotransmitter 5-ht2 receptor Pharmacology
Citations 141
Key findings Forepaw treading induced by 5-MeODMT is mediated by the 5-HT1A receptor, not by 5-HT2, dopamine, or beta-adrenoceptors.

Abstract

The 5-HT receptor subtypes involved in the mediation of reciprocal forepaw treading and the flat body posture induced by the central 5-HT receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), were examined in intact rats and in rats depleted of monoamines with reserpine. Forepaw treading in non-reserpinised rats was antagonised by the 5-HT2 receptor antagonist, ketanserin, only at doses in excess of those required for occupation of a large proportion of 5-HT2 receptors in brain, and at which there was significant inhibition of stereotyped sniffing induced by the dopamine receptor agonist, apomorphine. Since forepaw treading induced by 5-MeODMT was also blocked in intact rats by haloperidol, blockade of the behaviour by ketanserin may more accurately reflect antagonism at dopamine receptors than at 5-HT2 receptors. In reserpinised rats, i.e. with minimised contributions from other monoamine systems, neither forepaw treading nor the flat body posture were significantly altered by ketanserin, haloperidol or the beta 1- and beta 2-selective adrenoceptor antagonists, betaxolol and ICI 118.551, making a key role for 5-HT2 receptors, dopamine receptors and beta-adrenoceptors unlikely. In contrast, forepaw treading in both reserpinised and non-reserpinised rats was antagonised stereoselectively by pindolol and by spiperone, which interact with 5-HT1 and 5-HT1A recognition sites. The results are consistent with the hypothesis that forepaw treading induced by 5-MeODMT arises by activation of the putative 5-HT1A receptor. Antagonism of the flat body posture by pindolol could be demonstrated only in non-reserpinised rats and the mechanism of induction of this behaviour remains to be established.

Comparable studies

Other preclinical and animal studies on 5-MeO-DMT, most cited first.

Study Year Design Participants
Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells 2014 In vitro study
Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats 2018 Experimental study
Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats 2006 Preclinical study
Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts 1998 Experimental study
N,N-dimethyltryptamine compound found in the hallucinogenic tea ayahuasca, regulates adult neurogenesis in vitro and in vivo Mice 2020 In vitro and in vivo experimental study

Citations in the library

Cited by 29

and 24 more in the library

Cites 3

Related reading

Explore topics

Serotonin 5-MeO-DMT DMT