University of Bordeaux, France; Centre National de la Recherche Scientifique (CNRS), Unit 5287, Institut des Neurosciences Intégratives et Cognitives d'Aquitaine (INCIA), Bordeaux, France.
2 papers in the library · 13 citations · publishing 2024-2025
Classical psychedelics, which bind to serotonin receptors (5-HTRs), have complex and region-specific effects on the activity of monoaminergic neurons. They can inhibit the firing of serotonergic neurons without necessarily reducing serotonin release in all brain regions, and similarly inhibit noradrenergic neuron spontaneous activity without consistently decreasing noradrenaline release. Their influence on dopaminergic systems is also complex, with opposing effects depending on the specific serotonin receptor subtype and the brain state. Overall, there is no single, clear neuronal signature for how psychedelics affect monoamine systems; instead, the effects are state-dependent and region-dependent.
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.