SLC6A4 binding site and acute prosocial effects of (+/-)-3,4-methylendioxymethamphetamine (MDMA) are evolutionarily conserved in Octopus bimaculoides

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.

Study at a glance

Abstract

Human and octopus lineages are separated by over 500 million years of evolution, and show divergent anatomical patterns of brain organization. Moreover, while humans exhibit highly complex social behaviors, octopuses are thought to be largely asocial and solitary. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species, and in many cases enable overlapping functions. Here we provide evidence that, as in humans, the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides, and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.