The Prosocial Effects of 3, 4-methylenedioxymethamphetamine (MDMA) in Squirrel Monkeys Open Access

Minerva, Adelaide Rose (2016)

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3, 4-methylenedioxymethamphetamine (MDMA; 'ecstasy') is a synthesized drug that shares structural and pharmacological similarities with both hallucinogens and stimulants, yet has unique effects on prosocial and affiliative behavior. Recreational MDMA users often report feelings of increased sociability, friendliness, euphoria, closeness to others, and empathy. In line with these findings, controlled laboratory studies demonstrate that the compound enhances social behaviors and information processing in both humans and rodents. Due to its prosocial effects, MDMA has been proposed as an adjunct to psychotherapy for individuals with treatment resistant social and anxiety conditions, such as post-traumatic stress disorder (PTSD) and autism. This study sought to better understand the neurobiological mechanisms behind the MDMA-induced increase in social behaviors. Four male squirrel monkeys of the black cap subspecies (Saimiri boliviensis) served as subjects throughout this experiment. We administered a low dose range (0, 0.01, 0.03, 0.1, 0.3 mg/kg) of MDMA with pretreatment of saline, M100907, a 5-HT2A receptor antagonist, or WAY163909, a 5-HT2C receptor agonist, to subjects twice per week in a laboratory setting. Behavior and vocalizations while on the drug in the lab were analyzed and conditions were compared to each other in order to better understand the mechanism by which MDMA elicits its prosocial effects. MDMA resulted in a dose-dependent increase in prosocial behavior and affiliative calls. Pretreatment with M100907 attenuated these effects, whereas pretreatment with WAY163909 did not have a statistically significant effect. These results suggest that the social effects may be mediated by a system involving the amygdala to reduce social fear rather than a dopaminergic reward system. With the findings of this investigation, we hope to contribute to the future creation of a novel therapeutic with these benefits to social behavior but without the negative side effects and potential neurotoxicity of MDMA.

Table of Contents

Hypothesis. 1

Purpose and Rationale. 1

Introduction. 3

Background and History of MDMA. 3

Animal Laboratory Studies. 6

Human Studies. 8

Structure and Mechanism of Action. 14

Neurotoxicity. 17

Materials and Methods. 20

Subjects. 20

Drugs. 20

Experimental Protocol. 22

Behavioral Scoring. 22

Vocalization Scoring. 23

Statistical Analysis. 24

Results. 25

Behavioral Results. 25

Vocalization Results. 27

Discussion. 29

Future Directions. 34

Limitations. 37

Conclusion. 39

Figures and Graphs. 40

Figure 1-MDMA, Methamphetamine, and Mescaline. 40

Table 1-Descriptive Statistics, One-Way Repeated Measures ANOVAs. 41

Table 2-Descriptive Statistics, Two-Way Repeated Measures ANOVAs. 42

Table 3-Descriptive Statistics, REML t-tests from a GLM regression. 43

Figure 2-MDMA Affiliative Behavior by Dose. 44

Figure 3-MDMA Affiliative Behavior by Dose and Monkey. 45

Figure 4-MDMA Number of Affiliative Calls. 46

Figure 5-MDMA Frequency of Call Types. 47

Figure 6-Methamphetamine Affiliative Behavior by Dose. 48

Figure 7-Methamphetamine Affiliative Behavior by Dose and Monkey. 49

Figure 8-Methamphetamine Number of Affiliative Calls. 50

Figure 9-Methamphetamine Frequency of Call Types. 51

Figure 10-M100907 and MDMA Affiliative Behavior by Dose. 52

Figure 11-M100907 and MDMA Number of Affiliative Calls. 53

Figure 12-M100907 and MDMA Frequency of Call Types. 54

Figure 13-WAY163909 and MDMA Affiliative Behavior by Dose. 55

Works Cited. 56

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