MDMA-induced indifference to negative sounds is mediated by the 5-HT receptor.

K P C Kuypers, R de la Torre, M Farre, N Pizarro, L Xicota, J G Ramaekers

Journal: Psychopharmacology 2018;235(2):481-490

PMID: 28735368

Abstract

BACKGROUND

MDMA has been shown to induce feelings of sociability, a positive emotional bias and enhanced empathy. While previous research has used only visual emotional stimuli, communication entails more than that single dimension and it is known that auditory information is also crucial in this process. In addition, it is, however, unclear what the neurobiological mechanism underlying these MDMA effects on social behaviour is. Previously, studies have shown that MDMA-induced emotional excitability and positive mood are linked to the action on the serotonin (5-HT) 2A receptor.

AIM

The present study aimed at investigating the effect of MDMA on processing of sounds (Processing of Affective Sounds Task (PAST)) and cognitive biases (Approach-Avoidance Task (AAT)) towards emotional and social stimuli and the role of 5-HT receptor in these effects.

METHODS

Twenty healthy recreational users entered a 2 × 2, placebo-controlled, within-subject study with ketanserin (40 mg) as pre-treatment and MDMA (75 mg) as treatment. Behavioural (PAST, AAT) measures were conducted 90 min after treatment with MDMA, respectively, 120 min after ketanserin. Self-report mood measures and oxytocin concentrations were taken at baseline and before and after behavioural tests.

RESULTS

Findings showed that MDMA reduced arousal elicited by negative sounds. This effect was counteracted by ketanserin pre-treatment, indicating involvement of the 5-HT receptor in this process. MDMA did not seem to induce a bias towards emotional and social stimuli. It increased positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal levels when listening to negative sounds was not related to the elevated subjective arousal.

CONCLUSION

It is suggested that this decrease in arousal to negative stimuli reflects potentially a lowering of defences, a process that might play a role in the therapeutic process.

Address: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. [email protected].; Integrative Pharmacology and Neurosciences Systems Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.; Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Santiago de Compostela, Spain.; CEXS-UPF, Universitat Pompeu Fabra, Barcelona, Spain.; Integrative Pharmacology and Neurosciences Systems Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.; Universitat Autonoma de Barcelona, Barcelona, Spain.; Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.; Integrative Pharmacology and Neurosciences Systems Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.; Universitat Autonoma de Barcelona, Barcelona, Spain.; Integrative Pharmacology and Neurosciences Systems Research Group, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.; Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands.
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