Skip to content

Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD)

Emmanuelle A. D. Schindler, Kuldip D. Dave, Elaine M. Smolock, Vincent J. Aloyo, John A. Harvey

Pharmacology, Biochemistry, and Behavior December 15, 2011 DOI: 10.1016/j.pbb.2011.12.002 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Animal study Peer reviewed
Population Rabbits
Interventions DOI LSD ritanserin ketanserin
Topics LSD Serotonin
Keywords Ritanserin Hallucinogen Ketanserin 5-ht2 receptor Receptor antagonist In vivo Neuropharmacology 5-HT Receptor
Citations 18
Key points Both DOI- and LSD-elicited head bob behavior in rabbits requires activation of serotonin 2A and dopamine D1 receptors, implicating these two receptors in the mechanism of action of hallucinogens.

Abstract

RationaleAfter decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however.ObjectivesTwo commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model.MethodRabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection.ResultsBoth DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor.ConclusionAlthough DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens.

Comparable studies

Other preclinical and animal studies on LSD, most cited first.

Study Year Design Participants
Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex Human embryonic kidney 293 cells stably expressing 5-HT2ARs; wild-type and 5-HT2AR... 2003 Experimental study
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide Rats 1968 Experimental study
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission Male mice 2021 Multidisciplinary experimental study with in vivo electrophysiology, optogenetics, behavioral paradigms, molecular biology, and conditional knockout mice
A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons 2023 Preclinical study

Citations in the library

Cited by 14

and 9 more in the library

Cites 18

and 13 more in the library

Related reading

Explore topics

LSD Serotonin