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3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A

Elizabeth G Pitts1, Adelaide R Minerva1, Erika B Chandler1

  • 1Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|April 21, 2017
PubMed

Insights

3,4-Methylenedioxymethamphetamine (MDMA) enhances social behavior in squirrel monkeys, mediated by serotonin 5-HT2A receptors. This research clarifies MDMA

Area of Science:

  • Neuroscience
  • Primate Behavior
  • Pharmacology

Background:

  • 3,4-Methylenedioxymethamphetamine (MDMA) is known to increase sociality in humans and rodents.
  • The precise neurochemical mechanisms, particularly involving serotonin (5-HT), underlying MDMA's prosocial effects remain poorly understood.
  • Nonhuman primate models offer unique advantages for studying these mechanisms, yet have not been utilized for MDMA's social effects.

Purpose of the Study:

  • To investigate the neurochemical mechanisms of MDMA's social effects in nonhuman primates.
  • To examine the specific roles of serotonin receptor subtypes in mediating MDMA-induced social behaviors.
  • To compare the social effects of MDMA with methamphetamine in squirrel monkeys.

Main Methods:

  • Behavioral and vocalization analyses were conducted on four group-housed squirrel monkeys.
  • Subjects received MDMA, its enantiomers, or methamphetamine, with and without pretreatments of 5-HT receptor antagonists and agonists.
  • Data were analyzed using linear mixed-effects models to determine statistical significance.

Main Results:

  • MDMA and its enantiomers significantly increased affiliative social behaviors and vocalizations in squirrel monkeys.
  • Methamphetamine exhibited only modest effects on affiliative behaviors.
  • Pretreatment with a 5-HT2A receptor antagonist and a 5-HT2C receptor agonist attenuated MDMA's prosocial effects, while a 5-HT1A antagonist did not alter vocalizations but increased social contact.

Conclusions:

  • Nonhuman primates demonstrate MDMA-specific increases in affiliative social behaviors, consistent with human and rodent findings.
  • MDMA-induced prosocial effects in this model are dependent on 5-HT2A receptor activity, but not 5-HT1A receptors.
  • Understanding these neurochemical pathways could inform the development of novel therapeutics targeting social behavior with fewer limitations.

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