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

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. ONE SENTENCE SUMMARY: Here we provide evidence that the atypical amphetamine derivative (+/-)-3,4-methylendioxymethamphetamine (MDMA) increases acute social approach behaviors in Octopus bimaculoides , a finding that is paralleled by the evolutionary conservation of the SLC6A4 binding site of MDMA.