Abstract

Although an octopus brain has neither a nucleus accumbens, nor a dorsal raphe, nor a cerebral cortex, recently we have shown that the acute prosocial effects of MDMA are recapitulated in Octopus bimaculoides, likely through conserved molecular mechanisms (Edsinger and Dölen, Current Biology, 2018). This finding suggests that 5-HT has served to mediate sociality since before the divergence of vertebrate and invertebrate lineages over 600 million years ago and that MDMA targets these ancient mechanisms. This finding suggests that despite the substantial differences in brain anatomy, deep homology enables conservation of brain functions triggered by psychedelics. A critical period is a developmental epoch during which the nervous system is expressly sensitive to specific environmental stimuli that are required for proper circuit organization and learning. In disease states, closure of critical periods limits the ability of the brain to adapt even when optimal conditions are restored. In this context, our discovery that the psychedelic drug, MDMA, but not the psychostimulant cocaine, is able to reopen the social reward learning critical period (Nardou et al., Nature, 2019) constitutes a breakthrough for translational neuroscience. Interestingly, these studies also demonstrate that MDMA-induced reopening of the critical period for social reward learning shares a number of features with the therapeutic effects of MDMA, including: rapid onset, durability beyond the acute effects of the drug, and dependence on social setting. Taken together, these observations provide support for the provocative idea that we may have discovered the long sought-after “master key” for unlocking critical periods across the brain.