PMID- 30172789 OWN - NLM STAT- MEDLINE DCOM- 20190213 LR - 20190215 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 837 DP - 2018 Oct 15 TI - 3,4-Methylenedioxymethamphetamine, mephedrone, and beta-phenylethylamine release dopamine from the cytoplasm by means of transporters and keep the concentration high and constant by blocking reuptake. PG - 72-80 LID - S0014-2999(18)30500-4 [pii] LID - 10.1016/j.ejphar.2018.08.037 [doi] AB - The addiction-related behavioural effects of drugs of abuse are mediated by the mesocorticolimbic monoamine systems. We investigated the effects of 3,4-methylenedioxymethamphetamine (MDMA), mephedrone, beta-phenylethylamine (beta-PEA) methylphenidate (MPH) on dopamine release from mouse perfused nucleus accumbens and prefrontal cortex slices. The fractional release of [(3)H]-dopamine was measured at rest and in response to field stimulation. The distributions of [(3)H]-dopamine and its metabolites were determined using high-pressure liquid chromatography. The effect of drugs on [(3)H]-dopamine uptake was measured in synaptosomal P2 preparations from the frontal cortex and striatum. Similar to MDMA, mephedrone beta-PEA increased the resting release of [(3)H]-dopamine from the nucleus accumbens and prefrontal cortex in a [Ca(2+)](o)-independent manner, and the stimulation-evoked release was also augmented. In contrast, MPH failed to affect the resting release but potentiated the release in response to axonal activity. Similar to dopamine transporter antagonist GBR 12909, mephedrone, MDMA and MPH biphasically inhibited the [(3)H]-dopamine uptake. The administration of GBR 12909 and nisoxetine, or lowering the bath temperature prevented MDMA, mephedrone and beta-PEA from enhancing the resting, cytoplasmic release of [(3)H]-dopamine, indicating the role of transporters in the release process. We conclude that amphetamine-like drugs of abuse and the trace amine beta-PEA excessively increase the [Ca(2+)](o)-independent, non-vesicular release of dopamine from the cytoplasm into the extrasynaptic space and inhibit the high-affinity transporters, thereby maintaining a high ambient, non-synaptic concentration of dopamine that may tonically control the activity of neurons equipped with dopamine receptors and is likely involved in the reinforcing effects and abusive potential of amphetamines. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zsilla, Gabriella AU - Zsilla G AD - Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: zsilla@koki.hu. FAU - Hegyi, Daniella E AU - Hegyi DE AD - Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: dahegyi@gmail.com. FAU - Baranyi, Maria AU - Baranyi M AD - Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: baranyi@koki.hu. FAU - Vizi, E Sylvester AU - Vizi ES AD - Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. Electronic address: esvizi@koki.mta.hu. LA - eng PT - Journal Article DEP - 20180830 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Phenethylamines) RN - 327C7L2BXQ (phenethylamine) RN - 44RAL3456C (Methamphetamine) RN - 8BA8T27317 (mephedrone) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - SY7Q814VUP (Calcium) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Animals MH - Calcium/physiology MH - Cytoplasm/*metabolism MH - Dopamine/*metabolism MH - Dopamine Plasma Membrane Transport Proteins/*physiology MH - Dopamine Uptake Inhibitors/*pharmacology MH - Male MH - Methamphetamine/*analogs & derivatives/pharmacology MH - Mice MH - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology MH - Nucleus Accumbens/metabolism MH - Phenethylamines/*pharmacology MH - Prefrontal Cortex/metabolism OTO - NOTNLM OT - Dopamine OT - MDMA OT - Mephedrone OT - Methylphenidate OT - Release OT - beta-phenylethylamine EDAT- 2018/09/03 06:00 MHDA- 2019/02/14 06:00 CRDT- 2018/09/03 06:00 PHST- 2018/03/28 00:00 [received] PHST- 2018/08/24 00:00 [revised] PHST- 2018/08/29 00:00 [accepted] PHST- 2018/09/03 06:00 [pubmed] PHST- 2019/02/14 06:00 [medline] PHST- 2018/09/03 06:00 [entrez] AID - S0014-2999(18)30500-4 [pii] AID - 10.1016/j.ejphar.2018.08.037 [doi] PST - ppublish SO - Eur J Pharmacol. 2018 Oct 15;837:72-80. doi: 10.1016/j.ejphar.2018.08.037. Epub 2018 Aug 30.