Ketamine, a mood-altering compound, suppresses passivity induced by futility in larval zebrafish, similar to effects in rodent learned helplessness models. Brain-wide imaging in behaving zebrafish shows ketamine elevates intracellular calcium in astroglia for many minutes, followed by persistent calcium downregulation after washout. This calcium elevation depends on astroglial α1-adrenergic receptors and is required for suppression of passivity. Chemo- and optogenetic experiments show that the aftereffects of glial calcium elevation are sufficient to suppress passivity by inhibiting neuronal-astroglial integration of behavioral futility. Imaging in mouse cortex reveals ketamine elevates astroglial calcium through conserved pathways, suggesting ketamine exerts its behavioral effects by persistently modulating evolutionarily ancient neuromodulatory systems spanning neurons and astroglia.
In a mouse model of peripartum mood disorder, a single dose of psilocybin did not improve impaired caregiving, maternal withdrawal, or anxiety-like behaviors; treated dams were more anxious and had increased risk of overall behavioral impairments two weeks after injection. In contrast, virgin female mice given the same dose showed reduced anxiety and lower risk of behavioral impairments. Additionally, a single postnatal exposure to psilocybin through breastmilk increased the risk of behavioral phenotypes related to mood and sociability disorders in both male and female offspring when they reached adulthood. These findings suggest psilocybin may pose risks during the postpartum period for mothers and their offspring.