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. 2019 Apr;35(3):594-605.
doi: 10.1007/s12640-018-9973-4. Epub 2018 Oct 30.

Methcathinone and 3-Fluoromethcathinone Stimulate Spontaneous Horizontal Locomotor Activity in Mice and Elevate Extracellular Dopamine and Serotonin Levels in the Mouse Striatum

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Free PMC article

Methcathinone and 3-Fluoromethcathinone Stimulate Spontaneous Horizontal Locomotor Activity in Mice and Elevate Extracellular Dopamine and Serotonin Levels in the Mouse Striatum

Jakub Wojcieszak et al. Neurotox Res. .
Free PMC article

Abstract

Methcathinone (MC) and 3-fluoromethcathinone (3-FMC) are well-known members of the synthetic cathinone derivatives, the second most abused group of novel psychoactive substances (NPS). They are considered as methamphetamine-like cathinones, as they elicit their psychostimulatory effects via inhibition of monoamine uptake and enhanced release. The present study examines the effects of MC and 3-FMC on the spontaneous locomotor activity of mice and extracellular levels of dopamine and serotonin in the mouse striatum. Both MC and 3-FMC produced a dose-dependent increase of horizontal locomotor activity, but no significant changes in rearing behavior were observed. The locomotor stimulation induced by MC and 3-FMC is mediated by activation of dopaminergic neurotransmission, as selective D1-dopamine receptor antagonist, SCH 23390, abolished the effects of both drugs. In line with pharmacological data obtained by previous in vitro studies, MC and 3-FMC produced potent increases of extracellular dopamine and serotonin levels in the mouse striatum. Taken together, results presented within this study confirm previous findings and expand our knowledge on the pharmacology of MC and 3-FMC along with their behavioral effects.

Keywords: 3-Fluoromethcathinone; Dopamine; Methcathinone; Microdialysis; Novel psychoactive substances; Serotonin; Spontaneous locomotor activity.

Conflict of interest statement

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The use of adult male C57BL/6J inbred mice for the experiments was approved by the Local Ethical Commission for Experimentations on Animals in Łódź and Kraków. This article does not contain any studies with human participants.

Figures

Fig. 1
Fig. 1
Structures of methcathinone and 3-fluoromethcathinone
Fig. 2
Fig. 2
Effects of methcathinone (MC; 1, 3, 10 mg/kg) and 3-fluoromethcathinone (3-FMC; 1, 3, 10 mg/kg) on the spontaneous horizontal (panels a, b, c) and vertical (panels e, f, g) activity of mice measured in 10-min bins, and on total horizontal (panel d) and vertical (panel h) locomotor activity during 120 min. Data presented as mean ± SEM (n = 8). ***P < 0.001; **P < 0.01; *P < 0.05 vs. vehicle; ###P < 0.001; ##P < 0.01; P < 0.05 MC vs. 3-FMC; ^^^P < 0.001; ^P < 0.05 vs. 1 mg/kg; &&&P < 0.001 vs. 3 mg/kg, Tukey’s post hoc test. For all analyses, the same control group was used; therefore, its data reappears on panels ac and eg
Fig. 3
Fig. 3
Effects of the SCH 23390 (SCH; 0.06 mg/kg) pretreatment followed by treatment with methcathinone (MC; 10 mg/kg) or 3-fluoromethcathinone (3-FMC; 10 mg/kg) on the horizontal activity of mice measured in 10-min bins (panels a and b, respectively), and on total horizontal activity during 120 min (panel c). Data presented as mean ± SEM (n = 8). ***P < 0.001; **P < 0.01 vs. vehicle; ###P < 0.001; ##P < 0.01; #P < 0.05 vs. SCH + MC or SCH + 3-FMC group, Tukey’s (panels a and b) or Sidak’s (panel c) post hoc test. For both compounds, one analysis containing single vehicle and single SCH group was performed. Separation of data into panels a and b was done in order to improve visual appearance; therefore, the same data reappears on panels a and b
Fig. 4
Fig. 4
Effects of methcathinone (MC; 3, 10 mg/kg) and 3-fluoromethcathinone (3-FMC; 3, 10 mg/kg) on the extracellular DA and 5-HT levels in the mouse striatum, shown as a time course (panels a, b, d, e) or an area under the curve, AUC (panels c, f). Drug administration is indicated with an arrow. Data presented as mean ± SEM (n = 6). ***P < 0.001 vs. control group; ###P < 0.001 3 mg/kg vs. 10 mg/kg; ^^^P < 0.001 MC vs. 3-FMC, Tukey’s post hoc test. For both drugs and doses, one control group was used; therefore, its data reappears on panels a and d, and b and e

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