Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive–compulsive disorder

Tarek Zghoul; Pierre Blier

doi:10.1017/s1461145702003218

Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive–compulsive disorder

Tarek Zghoul, Pierre Blier

The International Journal of Neuropsychopharmacology March 1, 2003 DOI: 10.1017/s1461145702003218 (opens in new tab)

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Study at a glance

AI-extracted from the abstract

Characteristics	Experimental study Peer reviewed
Population	Rats
Intervention	LSD
Dose	100 microg/kg i.p. once daily for 4 days
Duration	4-day intervention, experiments 24 h after last dose
Topics	Serotonin LSD
Keywords	Hippocampus Hallucinogen Inhibitory postsynaptic potential Psychotomimetic Premovement neuronal activity Pharmacology Obsessive-compulsive spectrum disorders
Citations	13
Key findings	LSD enhances the inhibitory effect of serotonin on orbitofrontal cortex neurons while reducing it in hippocampal neurons, suggesting a potential mechanism for anti-OCD effects.

Abstract

Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

Comparable studies

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Study	Year	Design
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

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