Fig. 4: Stereospecific effect of cathinones on SERT-dependent 5-HT release in vivo.
From: Serotonin-releasing agents with reduced off-target effects
a Schematics of optic probe placement in the NAc of freely moving mice to assess extracellular 5-HT using a genetically encoded sensor. CPu = caudate putamen. b Representative single traces displaying the effect of saline (SAL) or D-FEN (3 or 10 mg kg−1, intraperitoneal injections at t = 120 s) on the relative fluorescence emitted by the 5-HT sensor. Data are shown as mean and standard deviation (N = 4 per condition). c Comparison of the effect of 3 and 10 mg kg−1 D-FEN on the sensor-emitted fluorescence versus saline control. Representative single traces showing changes in sensor-derived fluorescence following intraperitoneal injections (at t = 600 s) of d SAL, fluoxetine (FLX, 10 mg kg−1), D-FEN (10 mg kg−1), e S-4-MC (5 mg kg−1) plus vehicle (=S-4-MC, dark green) or S-4-MC (5 mg kg−1) plus FLX (10 mg kg−1) (=S-4-MC + FLX, light green), f S-4-TFMMC (10 mg kg−1) plus vehicle (=S-4-TFMMC, dark blue) or S-4-TFMMC (10 mg kg−1) plus FLX (10 mg kg−1) (=S-4-TFMMC + FLX, light blue) and g R-4-MC (5 mg kg−1) and R-4-TFMMC (10 mg kg−1). h Comparison of drug induced changes in fluorescence (N = 5 per condition). i Cartoon depicting guide cannula (blue column) and active microdialysis membrane (red tip, active length of 1 mm) placement in the NAc. j, k Effect of intraperitoneal S-4-MC (5 mg kg−1) on extracellular 5-HT and dopamine (DA) in presence or absence of co-administered fluoxetine (FLX, 10 mg kg−1) or vehicle. * denotes p ≤ 0.05 (Bonferroni’s) at the corresponding timepoint l fold increase in extracellular 5-HT and DA at t = 160 min relative to baseline (t = 0–80 min) as shown in j and k. One-sample t-test versus the hypothetical mean of 1 (*p ≤ 0.05). Data are shown as mean and standard deviation. Data in b, c, h, j, k and l are given as mean and standard deviation. Data in c and h were analyzed using Kruskal–Wallis, followed by Dunn’s multiple comparison test. *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001 versus SAL. Detailed sample sizes are given in the Supplementary Information.
