3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner
Elizabeth G Pitts, Adelaide R Minerva, Erika B Chandler, Jordan N Kohn, Meghan T Logun, Agnieszka Sulima, Kenner C Rice, Leonard L Howell
Neuropsychopharmacology September 1, 2017 DOI: 10.1038/npp.2017.80 via Springer Nature
Summary
MDMA and its enantiomers increase affiliative social behaviors and vocalizations in group-housed squirrel monkeys, while methamphetamine has only modest effects. Pretreatment with a 5-HT_2A receptor antagonist or a 5-HT_2C receptor agonist reduces MDMA-induced social behaviors, whereas a 5-HT_1A receptor antagonist does not affect affiliative vocalizations and even increases social contact. These results indicate that the prosocial effects of MDMA depend on 5-HT_2A, but not 5-HT_1A, receptors, aligning with findings in humans and rodents. Understanding these neurochemical mechanisms may aid in developing therapeutics that retain MDMA's social benefits with fewer drawbacks.
Study at a glance
| Characteristics | Observational study with drug administration and behavioral analysis Peer reviewed |
|---|---|
| Sample size | 4 |
| Population | Group-housed squirrel monkeys |
| Citations | 20 |
| Key finding | MDMA increases affiliative social behaviors and vocalizations in squirrel monkeys via 5-HT_2A receptor-dependent mechanisms, while 5-HT_1A receptors are not required for these effects. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) increases sociality in humans and animals. Release of serotonin (5-HT) is thought to have an important role in the increase in social behaviors, but the mechanisms underlying these effects are poorly understood. Despite the advantages of nonhuman primate models, no studies have examined the mechanisms of the social effects of MDMA in nonhuman primates. The behavior and vocalizations of four group-housed squirrel monkeys were examined following administration of MDMA, its enantiomers, and methamphetamine. 5-HT receptor antagonists and agonists were given as drug pretreatments. Data were analyzed using linear mixed-effects models. MDMA and its enantiomers increased affiliative social behaviors and vocalizations, whereas methamphetamine had only modest effects on affiliative behaviors. Pretreatment with a 5-HT_2A receptor antagonist and a 5-HT_2C receptor agonist attenuated the MDMA-induced increase in social behaviors, while a 5-HT_1A receptor antagonist did not alter affiliative vocalizations and increased MDMA-induced social contact. Nonhuman primates show MDMA-specific increases in affiliative social behaviors following MDMA administration, in concordance with human and rodent studies. MDMA-induced increases in social behaviors are 5-HT_2A, but not 5-HT_1A, receptor dependent. Understanding the neurochemical mechanisms mediating the prosocial effects of MDMA could help in the development of novel therapeutics with the unique social effects of MDMA but fewer of its limitations.