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Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor.

R. Grailhe, C. Waeber, S. Dulawa, J. Hornung, X. Zhuang, D. Brunner, Mark A. Geyer, R. Hen

Neuron March 1, 1999 DOI: 10.1016/s0896-6273(00)80712-6 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational study (genetic knockout model) Peer reviewed
Population Wild-type and 5-HT5A knockout mice
Intervention LSD
Measures exploratory activity, anxiety-related behaviors
Topics LSD Serotonin
Key findings Knockout mice lacking the 5-HT5A receptor showed increased exploratory activity in novel environments but no change in anxiety-related behaviors, and the stimulatory effect of LSD on exploratory activity was attenuated. This suggests that 5-HT5A receptors modulate exploratory behavior and may mediate some psychotropic effects of LSD.

Abstract

In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A-KO mice displayed increased exploratory activity but no change in anxiety-related behaviors. In addition, the stimulatory effect of LSD on exploratory activity was attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate the activity of neural circuits involved specifically in exploratory behavior and suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A receptors.

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

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