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Curr Biol. 2017 Feb 6;27(3):451-457. doi: 10.1016/j.cub.2016.12.030. Epub 2017 Jan 26.

The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation.

Author information

1
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland. Electronic address: preller@bli.uzh.ch.
2
Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
3
Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
4
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland; MR Center of the Psychiatric University Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
5
Psychopharmacology Research, Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Hebelstrasse 2, 4031 Basel, Switzerland.
6
Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.

Abstract

A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HT2AR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HT2AR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.

KEYWORDS:

dopamine; ketanserin; lysergic acid diethylamide; meaning; music; personal relevance; serotonin 2A receptor

PMID:
28132813
DOI:
10.1016/j.cub.2016.12.030
[Indexed for MEDLINE]
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