Nature communications
June 10, 2024
Andiara E Freitas, Bo Feng, Timothy Woo et al.
9 citations
A single low dose of ketamine produces both immediate and lasting antidepressant effects, linked to the repair of glutamatergic synapses in the medial prefrontal cortex. In a mouse model of chronic stress, ketamine altered multiple molecular pathways. Cell-cell communication analyses predicted that planar-cell-polarity (PCP) signaling decreased after chronic corticosterone treatment but increased after ketamine in most excitatory neurons. Similar PCP signaling reductions were predicted in the dorsolateral prefrontal cortex of people with major depressive disorder. Neurons connecting the infralimbic prefrontal cortex to the basolateral amygdala regulated immobility and food intake. Knocking out specific PCP proteins in these neurons blocked ketamine's synapse restoration and behavioral improvements, indicating that PCP proteins in this circuit mediate ketamine's effects.
The international journal of biochemistry & cell biology
November 1, 2024
Jasmine Jade Butler, Daria Ricci, Chloé Aman et al.
8 citations
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.
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.