Dataset Information

3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner.

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.

SUBMITTER: Pitts EG

PROVIDER: S-EPMC5561347 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner.

Pitts Elizabeth G EG Minerva Adelaide R AR Chandler Erika B EB Kohn Jordan N JN Logun Meghan T MT Sulima Agnieszka A Rice Kenner C KC Howell Leonard L LL

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20170420 10

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 administrat ...[more]

PMID: 28425496

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Project description:Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking - an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected), and blissful state (p < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness.

Dataset Information

3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner.

Publications

3,4-Methylenedioxymethamphetamine Increases Affiliative Behaviors in Squirrel Monkeys in a Serotonin 2A Receptor-Dependent Manner.

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