5-HT2A receptors shape whole-brain monoaminergic coherence in male mice.
Progress in neuro-psychopharmacology & biological psychiatry July 13, 2025 Jasmine Jade Butler, Margherita Virgili, Giuseppe Di Giovanni et al. 5 citations
Serotonergic psychedelics disrupt the normally organized pattern of correlations among serotonin, dopamine, and noradrenaline concentrations across 28 brain regions in mice during forced exploratory behavior. Both the 5-HT2A receptor agonist TCB-2 and the antagonist MDL-100,907 decreased correlations between regional neurochemical levels, while combining them partially restored those correlations. TCB-2 dose-dependently reduced serotonin turnover across all brain regions and dopamine turnover in the striatum, and enhanced markers of dopamine and noradrenaline systems in the anterior cingulate cortex. MDL-100,907 alone had minimal effects on monoamine levels but reduced TCB-2-induced head twitches and increased monoamine concentrations in the anterior cingulate cortex without affecting the serotonin turnover decrease. The functional connectivity of monoaminergic systems during exploration is highly sensitive to modulation through 5-HT2A receptor activation or blockade.