Fig. 1: MDMA engages distinct reward processes.
From: 5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA
a Schematic of 3-chamber social preference test. b Effect of FEN (10 mg/kg), MDMA (7.5 mg/kg), MDMA (15 mg/kg), and METH (2 mg/kg) on social preference in the 3-chamber test. Unpaired, two-tailed t-test – FEN: t19 = 2.946, **p = 0.0083,MDMA (7.5 mg/kg): t20 = 2.746, *p = 0.0125. MDMA (15 mg/kg): t10 = 4.442, **p = 0.0012. METH (2 mg/kg): t20 = 0.921, p = 0.3681. c Summary of social preference across different drugs. Ordinary one-way ANOVA, F4,72 = 12.55, ****p < 0.0001. Tukey’s multiple comparisons test, saline vs FEN ***p = 0.0004, saline vs MDMA 7.5 ***p = 0.0001, saline vs MDMA 15 ****p < 0.0001, saline vs METH p = 0.9609, FEN vs METH **p = 0.0094, MDMA 7.5 vs METH **p = 0.0091, MDMA 15 vs METH ***p = 0.0008. d Schematic of drug conditioned place preference (CPP) testing and protocol. e Preference for each drug-paired context for each drug. Saline: paired, two-tailed t-test, t7 = 1.799, p = 0.115. FEN: paired, two-tailed t-test, t10 = 0.739, p = 0.4768. MDMA 7.5: paired, two-tailed t-test, t11 = 1.459, p = 0.1726. MDMA 15: paired, two-tailed t-test, t13 = 3.672, **p = 0.0028. METH 2: paired, two-tailed t-test, t7 = 3.714, **p = 0.0075. f Summary and direct comparison of CPP scores between drug groups. Ordinary one-way ANOVA, F4,48 = 6.965, ***p = 0.0002. Dunnett’s multiple comparisons test, saline vs FEN p = 0.3741, saline vs MDMA 7.5 p = 0.267, saline vs MDMA 15 **p = 0.0022, saline vs METH 2 ***p = 0.0003. g Configuration of fiber photometry recording with GRABDA in the NAc medial shell of wild-type mice. Scale = 100 μm. h Time course of bulk DA release triggered by each drug. i Summary of area under the curve of DA release for each drug at the specified dose. Repeated measures one-way ANOVA, F4,20 = 11.06, ****p < 0.0001. Tukey’s multiple comparisons test, saline vs FEN 10 p = 0.9734, saline vs MDMA 7.5 p = 0.0812, saline vs MDMA 15 ***p = 0.0004, saline vs METH 2 ***p = 0.0009. j Configuration of fiber photometry recording with GRAB5-HT in the NAc medial shell of wild-type mice. Scale = 100 μm. k Time course of bulk 5-HT release triggered by each drug. l Summary of area under the curve of 5-HT release for each drug at the specified dose. Repeated measures one-way ANOVA, F2,6 = 103.4, ****p < 0.0001. Tukey’s multiple comparisons test, saline vs MDMA 7.5 ****p < 0.001, saline vs METH 2 ***p = 0.0007, MDMA 7.5 vs METH 2 ***p = 0.0003.
