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Fourteen TAAR1 agonists emerge with high brain exposure and potencies, with one compound showing potency comparable to the investigational drug ulotaront and two compounds exhibiting even greater potency, at levels sufficient for behavioral studies.
Microglial dectin-1 exerts age-dependent effects: beneficial for amyloid pathology in mid-life but detrimental for cognition and anxiety-related behavior in later life, highlighting the need to consider age, the cell types expressing dectin-1, and dectin-1-activating ligands.
E engineered HTR2A mouse lines enabling in vivo mapping, targeting and modulation of receptor-expressing neurons are developed and validated their utility across biochemical, electrophysiological and behavioral studies of psychedelic mechanisms.
Cell-type-specific opioid blockade in accumbal cholinergic interneurons abolishes morphine-reward learning without impairing analgesia and decouples morphine-evoked dopamine elevations from acetylcholine dips, suggesting pro-cholinergic strategies to limit early opioid reward acquisition.
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