Effect of Some Psychoactive Drugs Used as 'Legal Highs' on Brain Neurotransmitters.

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

doi:10.1007/s12640-015-9569-1

Krystyna Gołembiowska, Katarzyna Kamińska + Show 3 more

Open Access

https://doi.org/10.1007/s12640-015-9569-1

Copy DOI

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.

Highlights

According to recent EMCDDA report, over the past 5 years, there has been an unprecedented increase in the number, type, and availability of new psychoactive substances in Europe, which replace their illegal counterparts and are obtainable on the Internet
We investigated the changes in DA and 5-HT release in striatum, nucleus accumbens septi, and frontal cortex, following single administration of pharmacologic and neurotoxic effects.4-Methoxyamphetamine (PMA), PMMA, and MEPH, in the adult rat model
DA release was enhanced by ca. 300–400 % of basal level in all studied brain regions at 60–80 min after administration. 5-HT release was increased by PMMA in both doses (5 and 10 mg/kg) by ca. 700, 1000, and 400 % of basal level at 40–100 min after administration in striatum, frontal cortex, and nucleus accumbens, respectively (Fig. 5)

Summary

Introduction

According to recent EMCDDA report, over the past 5 years, there has been an unprecedented increase in the number, type, and availability of new psychoactive substances in Europe, which replace their illegal counterparts and are obtainable on the Internet. 4-Methoxyamphetamine (PMA) and 4-methoxy-N-methylamphetamine (PMMA) are methoxylated phenylethylamine derivatives first encountered on the illegal market in 1970s Because of their similarity to 3,4-methylenedioxymethamphetamine (MDMA) and replacing it in ‘‘ecstasy’’ tablets, they are widespread among young people and consumed without any safe testing (Daws et al 2000). Studies in rodents suggest that PMA and PMMA are capable of producing acute serotonergic as well as dopaminergic neurotoxicity, they are less potent than MDMA, which produces dose-dependent selective degeneration of 5-HT terminals in just 7 days after administration (Battaglia et al 1987; Gough et al 2002; Gudelsky and Yamamoto 2003; Molliver et al 1990; Steele et al 1992)

Objectives

Methods

Results

Conclusion