---
title: "Diurnal and Seasonal Variation in Brain mu-Opioid and Dopamine D2 Receptor Signaling"
id: "biorxiv-6-diurnal-and-seasonal-regulation-of-brain-mu-opioid-and-dopamine-d2-receptor"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-6-diurnal-and-seasonal-regulation-of-brain-mu-opioid-and-dopamine-d2-receptor"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.01.748534v1?rss=1"
published_at: "2026-09-04T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Diurnal and Seasonal Variation in Brain mu-Opioid and Dopamine D2 Receptor Signaling
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-6-diurnal-and-seasonal-regulation-of-brain-mu-opioid-and-dopamine-d2-receptor
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.01.748534v1?rss=1)
- **Published At:** 2026-09-04T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study analyzed historical PET data to examine daily and seasonal rhythms in human neurotransmission, focusing on **mu-opioid receptor (MOR)** and **dopamine D2 receptor (D2R)** availability. - Scans included 188 healthy participants with [11C]carfentanil for MOR and 184 with [11C]raclopride for D2R. - Time-of-day (TOD) of scanning was used as the primary predictor of receptor availability to assess diurnal patterns. - Results showed an afternoon increase in **MOR availability** and an afternoon decrease in **D2R availability** compared with morning scans, indicating opposing diurnal trajectories for the two systems. - Seasonal variation (daylength) modulated the TOD effect for **MOR** but not for **D2R**, with MOR changes spanning anterior cingulate, dorsomedial and dorsolateral prefrontal cortex, insula, and striatum. - The diurnal variation in MOR availability within those regions was also sensitive to participants’ trait-anxiety levels. - Authors conclude that opioidergic and dopaminergic neurotransmission display distinct daily rhythms and that the MOR system uniquely mediates both diurnal and seasonal regulation and relates to behavioral trait measures. - The article is a preprint; the authors declared no competing interests and reported multiple funders. Specific numerical effect sizes, statistical parameters, and detailed methods beyond the PET tracers, sample sizes, and predictors were not reported in the supplied source text.
## Clinical Analysis & Structured Key Points
Diurnal and seasonal regulation of brain mu-opioid and dopamine D2 receptor signalling in humans | bioRxiv Skip to main content New Results Diurnal and seasonal regulation of brain mu-opioid and dopamine D2 receptor signalling in humans View ORCID Profile Michal Rafal Zareba , View ORCID Profile Juha Rinne , View ORCID Profile Jarmo Hietala , View ORCID Profile Pirjo Nuutila , View ORCID Profile Lauri Nummenmaa , View ORCID Profile Lihua Sun doi: https://doi.org/10.64898/2026.09.01.748534 Michal Rafal Zareba 1 Universitat Jaume I; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Michal Rafal Zareba For correspondence: michal.rafal.zareba{at}gmail.com Juha Rinne 2 University of Turku Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Juha Rinne Jarmo Hietala 2 University of Turku Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jarmo Hietala Pirjo Nuutila 2 University of Turku Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Pirjo Nuutila Lauri Nummenmaa 2 University of Turku Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lauri Nummenmaa Lihua Sun 2 University of Turku Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Lihua Sun Abstract Info/History Metrics Supplementary material Preview PDF Abstract Purpose: Rhythmic regulation of human neurotransmission systems, particularly the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) signaling, remains poorly understood. Although prior studies indicate possible diurnal fluctuations in D2R signaling, potential existence of diurnal rhythms in MOR signaling has yet to be investigated. Furthermore, whether and how seasonal factors may override or interact with diurnal rhythms in either system remains unexplored. Decoding these temporal dynamics and their possible links to behavioral traits, such as anxiety, may improve mood regulation models and inspire rhythm-tailored interventions. Methods: Based on a historical PET database of healthy humans scanned with [11C]carfentanil (n = 188) and [11C]raclopride (n = 184), we investigated the diurnal patterns of MOR and D2R availability in the brain, using time-of-day (TOD) of scanning as predictor. Furthermore, we examined whether the TOD differences in receptor availability were modulated by seasonal differences in the daylength (D2R and MOR) and trait-anxiety (MOR). Results: The data revealed increased MOR and decreased D2R availability in the afternoon compared to the morning scans. Interaction with the seasonal effect was, however, observed only for MOR availability, spanning brain areas including anterior cingulate, dorsomedial and dorsolateral prefrontal cortex, insula and striatum. Besides, the diurnal variation of MOR availability in these regions was also sensitive to trait-anxiety levels. Conclusions: The current results reveal the diurnal patterns in opioidergic and dopaminergic neurotransmission with an opposing trajectory. Furthermore, the data highlight a unique role of the MOR system, mediating both types of rhythmic regulations, as well as behavioral traits. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Balaguer Gonel Hermanos Foundation Jane and Aatos Erkko Foundation, https://ror.org/03vxy9y38 Gyllenberg’s Stiftelse The Finnish Governmental Research Funding for Turku University Hospital and for the Western Finland collaborative area European Research Council, https://ror.org/0472cxd90 , Advanced Grant #101141656 Diabetes Research Foundation in Finland Fudan University affiliated Huashan Hospital Starting Fund , 30302171001 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Next Posted September 04, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share Diurnal and seasonal regulation of brain mu-opioid and dopamine D2 receptor signalling in humans Michal Rafal Zareba , Juha Rinne , Jarmo Hietala , Pirjo Nuutila , Lauri Nummenmaa , Lihua Sun bioRxiv 2026.09.01.748534; doi: https://doi.org/10.64898/2026.09.01.748534 Share This Article: Copy Citation Tools Diurnal and seasonal regulation of brain mu-opioid and dopamine D2 receptor signalling in humans Michal Rafal Zareba , Juha Rinne , Jarmo Hietala , Pirjo Nuutila , Lauri Nummenmaa , Lihua Sun bioRxiv 2026.09.01.748534; doi: https://doi.org/10.64898/2026.09.01.748534 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (7962) Biochemistry (18614) Bioengineering (14760) Bioinformatics (44108) Biophysics (22441) Cancer Biology (19580) Cell Biology (26727) Clinical Trials (138) Developmental Biology (13895) Ecology (20878) Epidemiology (2067) Evolutionary Biology (25307) Genetics (16093) Genomics (23382) Immunology (18587) Microbiology (42208) Molecular Biology (17937) Neuroscience (92823) Paleontology (693) Pathology (2967) Pharmacology and Toxicology (5060) Physiology (8054) Plant Biology (15897) Scientific Communication and Education (2091) Synthetic Biology (4536) Systems Biology (10180) Zoology (2375)
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