The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats.

Publisher: Springer Country of Publication: United States NLM ID: 100929017 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-3524 (Electronic) Linking ISSN: 10298428 NLM ISO Abbreviation: Neurotox Res Subsets: MEDLINE

Publication: <2009-> : New York : Springer
Original Publication: [Amsterdam?] : Harwood Academic Publishers,

Brain/*drug effects ; Brain/*metabolism ; Central Nervous System Stimulants/*toxicity ; Methamphetamine/*analogs & derivatives ; Neurotoxicity Syndromes/*etiology ; Neurotoxicity Syndromes/*pathology ; Synaptic Transmission/*drug effects; Age Factors ; Analysis of Variance ; Animals ; Comet Assay ; Disease Models, Animal ; Dopamine/metabolism ; Glutamic Acid/metabolism ; Male ; Methamphetamine/toxicity ; Microdialysis ; Rats ; Rats, Wistar ; Serotonin/metabolism

According to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft. In animal studies, high repeated doses of mephedrone given to adolescent but not adult mice or rats induced toxic changes in 5-hydroxytryptamine (5-HT) neurons. The aim of our study was to investigate the effects of mephedrone given in adolescence on brain neurotransmission and possible neuronal injury in adult rats. Adolescent male rats were given mephedrone (5 mg/kg) for 8 days. In vivo microdialysis in adult rats showed an increase in dopamine (DA), 5-HT, and glutamate release in the nucleus accumbens and frontal cortex but not in the striatum in response to challenge dose in animals pretreated with mephedrone in adolescence. The 5-HT and 5-hydroxyindoleacetic acid contents decreased in the striatum and nucleus accumbens while DA turnover rates were decreased in the striatum and nucleus accumbens. The oxidative damage of DNA assessed with the alkaline comet assay was found in the cortex of adult rats. Therefore, the administration of repeated low doses of mephedrone during adolescence does not seem to induce injury to 5-HT and DA neurons. The oxidative stress seems to be responsible for possible damage of cortical cell bodies which causes maladaptive changes in serotonergic and dopaminergic neurons.

Erratum in: Neurotox Res. 2019 Jul;36(1):218. doi: 10.1007/s12640-019-00023-z. (PMID: 30905052)

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2013/09/B/NZ7/04104 Narodowe Centrum Nauki

Keywords: Adolescence; Mephedrone; Microdialysis; Neurotoxicity; Neurotransmitters

0 (Central Nervous System Stimulants)
333DO1RDJY (Serotonin)
3KX376GY7L (Glutamic Acid)
44RAL3456C (Methamphetamine)
8BA8T27317 (mephedrone)
VTD58H1Z2X (Dopamine)

Date Created: 20180502 Date Completed: 20181106 Latest Revision: 20240716

20240716

PMC6154178

10.1007/s12640-018-9908-0

29713996