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A 180-year-old drug may be the fastest depression treatment ever discovered | A new study shows that nitrous oxide may provide fast relief for those struggling with depression when traditional treatments fail.


The neural mechanisms underlying the antidepressant effects of nitrous oxide remain poorly understood. This study reveals that specific activation of layer V pyramidal neurons in the cingulate cortex rescues stress-associated hypoactivity states and is driven by inhibition of calcium-sensitive potassium channels rather than NMDA-receptor antagonism.

Using in vivo calcium imaging across Cg1 cortical layers and cell types in mice exposed to chronic stress, we show that subhypnotic N 2 O induces rapid and specific activation of L5 neurons that persists long after N 2 O clearance from the animal. Dysfunctional stress-sensitive circuits could require transient drug-induced changes in inhibition to allow selective patterns of excitatory activity to propagate through cortex and engage rapid and durable forms of activity-dependent synaptic plasticity (Supplementary Fig. Mice received N 2 O (25, 50, 75 %; Airgas) mixed with O 2(blended by Matrx MDS VMC anesthesia machine) or pure O 2(100%) via nose cone under the two-photon microscope, and the same cortical regions were reimaged based on blood vessel maps.

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