Molecular pathways implicated in antidepressant actions exhibits diurnal fluctuations in the prefrontal cortex and hippocampus of adult male and female mice
Year: 2026
Type: article
Abstract: ABSTRACT Epidemiological and experimental studies have demonstrated a bidirectional relationship between mood disorders and the circadian system, with disrupted circadian rhythms contributing to depressive states, and their restoration playing a key role in antidepressants effects. In this context, we sought to examine whether selected molecular pathways implicated in antidepressant responses exhibit diurnal regulatory patterns. Naïve adult male and female C57BL/6 mice were euthanized at 3-hour intervals beginning at Zeitgeber Time 0 (ZT0), and hippocampal (HC) and medial prefrontal cortex (mPFC) tissues were collected for RT-qPCR and western blot analyses. We observed statistically significant diurnal rhythmicity in all analyzed transcripts ( cFos , Arc , Nr4a1 , Dusp1 , Dusp5 , and Dusp6 ) in both HC and mPFC samples, with peak expression occurring during the dark (active) phase (ZT15–18). Phosphorylation levels of TrkB Y816 (tropomyosin-related kinase) and GSK3β S9 (glycogen synthase kinase 3β) also showed patterns suggestive of temporal rhythmicity, peaking during the light (inactive) phase. Levels of p-ERK2 T185/Y187 (extracellular-signal regulated kinase) did not display rhythmic fluctuations, but peaked during the light phase in the HC, especially in males. Collectively, these findings demonstrate that antidepressant-related signaling is subject to diurnal regulation, highlighting the importance of integrating circadian biology and time-of-day as relevant variables in the development of translationally relevant antidepressant research.
Source: Neuropharmacology
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,300
OpenAlex ID: W7220965849