Psychedelic drugs share the ability to reopen a critical period for social reward learning in adult mice, and the duration of this reopening matches the length of subjective effects in humans. The reinstatement of social reward learning is accompanied by a metaplastic restoration of oxytocin-mediated long-term depression in the nucleus accumbens. Analysis of gene expression in the open versus closed state indicates that reorganization of the extracellular matrix is a common downstream mechanism. These findings suggest a unifying mechanism for psychedelics' therapeutic properties and may guide clinical use and drug design for neuropsychiatric diseases.
MDMA, also known as ecstasy, increases social behavior in octopuses, despite over 500 million years of evolutionary separation from humans. Octopuses are typically solitary, but when given MDMA, they spent more time in close contact with other octopuses. This effect is linked to a shared serotonin transporter protein, which has a binding site for MDMA that is evolutionarily conserved in the octopus genome. The findings suggest that the neural systems underlying social behavior, particularly those involving serotonin, are ancient and have been preserved across diverse animal lineages.