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Effect of Some Psychoactive Drugs Used as ‘Legal Highs’ on Brain Neurotransmitters

Krystyna Gołembiowska, Alexandra Jurczak, Katarzyna Kamińska, Karolina Noworyta-Sokołowska, Anna Górska

Neurotoxicity Research April 1, 2016 DOI: 10.1007/s12640-015-9569-1 via Springer Nature

Summary

AI-generated from the abstract

New psychoactive designer drugs like PMA, PMMA, and mephedrone, which are used as substitutes in ecstasy pills, increase the release of dopamine and serotonin in rat brain regions including the striatum, nucleus accumbens, and frontal cortex, similar to MDMA. The drugs also altered tissue levels of these neurotransmitters in region-specific ways: for example, mephedrone and PMMA increased dopamine in the striatum, while mephedrone and PMMA decreased dopamine in the frontal cortex. These changes suggest the drugs may have dependence potential, though further research is needed to assess neurotoxicity and abuse risk.

Study at a glance

Characteristics Experimental study Peer reviewed
Population Rat brain
Interventions PMA PMMA MEPH MDMA
Dose PMA 5 and 10 mg/kg, PMMA 5 and 10 mg/kg, MEPH 5, 10 and 20 mg/kg, MDMA 5 and 10 mg/kg
Topics MDMA Serotonin
Keywords Mephedrone Pma Pmma Da
Key finding PMA, PMMA, and mephedrone enhance the release of dopamine and serotonin in rat striatum, nucleus accumbens, and frontal cortex, similar to MDMA.

Abstract

New psychoactive “designer drugs” are synthetic compounds developed to provide similar effects to illicit drugs of abuse, but not subjected to legal control. The rapidly changing legal status of novel psychoactive drugs triggers the development of new compounds, analogs of well-known amphetamine or mescaline. New designer drugs used as substitutes in ecstasy pills are the least investigated and can cause life-threatening effects on users. The aim of our research was to examine the effects of acute administration of 4-methoxyamphetamine (PMA, 5 and 10 mg/kg), 4-methoxy- N -methylamphetamine (PMMA, 5 and 10 mg/kg), and mephedrone (MEPH, 5, 10 and 20 mg/kg) on extracellular and tissue level of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites in rat brain, by microdialysis method in freely moving animals and HPLC. Similarly to 3,4-methylenedioxymethamphetamine (MDMA, 5 and 10 mg/kg) PMA, PMMA and MEPH enhanced the release of DA and 5-HT in rat striatum, nucleus accumbens, and frontal cortex. DA tissue content was increased by MEPH and PMMA in striatum, by MEPH, PMA, and PMMA in nucleus accumbens, and by PMA in frontal cortex. Instead, cortical DA level was decreased by MEPH and PMMA. MEPH did not influence 5-HT tissue level in striatum and nucleus accumbens, but decreased its level in frontal cortex. PMMA increased 5-HT content in striatum, while PMA enhanced it in nucleus accumbens and frontal cortex. Observed changes in brain monoamines and their metabolites by new psychoactive drugs suggest that these drugs may be capable of development of dependence. Further experiments are needed to fully investigate the neurotoxic and abuse potential of those drugs.

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