Psychopharmacology
May 1, 2005
Yong Zhang, Eduardo R Butelman, Stefan D Schlussman et al.
198 citations
Salvinorin A, a hallucinogen from Salvia divinorum, is a potent kappa opioid receptor agonist. In mice, higher doses (1.0 and 3.2 mg/kg) significantly decreased dopamine levels in the caudate putamen but not in the nucleus accumbens, an effect blocked by a kappa opioid receptor antagonist. These same doses caused conditioned place aversion and reduced locomotor activity. The findings suggest that salvinorin A's reduction of striatal dopamine may contribute to its aversive and motor-suppressing effects, consistent with its in vitro characterization as a kappa opioid receptor agonist.
Nature neuroscience
July 1, 2025
Ya'El Courtney, Joshua P Head, Neil Dani et al.
10 citations
The choroid plexus (ChP) regulates cerebrospinal fluid (CSF) composition, providing essential molecular cues for brain development. Apocrine secretion by embryonic ChP epithelial cells is a key regulator of the CSF proteome and neurodevelopment in male and female mice. Activation of serotonergic 5-HT2C receptors triggers sustained calcium signaling, driving high-volume apocrine secretion in mouse and human ChP. This secretion alters the CSF proteome, stimulating neural progenitors and shifting their developmental trajectory. Inducing ChP secretion in utero disrupts neural progenitor dynamics, cerebral cortical architecture, and offspring behavior. Illness or lysergic acid diethylamide exposure during pregnancy provokes coordinated ChP secretion in mouse embryos. The findings reveal a fundamental secretory pathway in the ChP that shapes brain development, and its disruption can have lasting consequences for brain health.
Biological psychiatry
June 13, 2025
Shaoqiang Han, Ya Tian, Huiting Yang et al.
1 citation
A systematic review of 18 multimodal neuroimaging studies (440 depressed individuals, 174 healthy controls) mapped brain locations linked to ketamine's antidepressant effects onto a functional brain network. The network primarily involved regions of the default mode, ventral attention, and frontoparietal networks. This network was robust under parameter perturbations and leave-one-study-out validation, and was specific to depression compared to other mental disorders. A ketamine-specific circuit, including the subgenual cingulate cortex and dorsolateral prefrontal cortex, overlapped with optimal brain stimulation sites for depression. These findings reconcile inconsistent results and suggest a network-level mechanism for ketamine's therapeutic effects.