Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.

Mephedrone (4-methylmethcathinone, MMC) is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar r...

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Main Authors: Craig P Motbey, Emily Karanges, Kong M Li, Shane Wilkinson, Adam R Winstock, John Ramsay, Callum Hicks, Michael D Kendig, Naomi Wyatt, Paul D Callaghan, Iain S McGregor
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3445542?pdf=render
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author Craig P Motbey
Emily Karanges
Kong M Li
Shane Wilkinson
Adam R Winstock
John Ramsay
Callum Hicks
Michael D Kendig
Naomi Wyatt
Paul D Callaghan
Iain S McGregor
author_facet Craig P Motbey
Emily Karanges
Kong M Li
Shane Wilkinson
Adam R Winstock
John Ramsay
Callum Hicks
Michael D Kendig
Naomi Wyatt
Paul D Callaghan
Iain S McGregor
author_sort Craig P Motbey
collection DOAJ
description Mephedrone (4-methylmethcathinone, MMC) is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar rats received single or repeated (once a day for 10 days) injections of MMC (30 mg/kg) or the comparator drug methamphetamine (METH, 2.5 mg/kg). Both MMC and METH caused robust hyperactivity in the 1 h following injection although this effect did not tend to sensitize with repeated treatment. Striatal dopamine (DA) levels were increased 1 h following either METH or MMC while striatal and hippocampal serotonin (5-HT) levels were decreased 1 h following MMC but not METH. MMC caused greater increases in 5-HT metabolism and greater reductions in DA metabolism in rats that had been previously exposed to MMC. Autoradiographic analysis showed no signs of neuroinflammation ([(125)I]CLINDE ligand used as a marker for translocator protein (TSPO) expression) with repeated exposure to either MMC or METH. In Experiment 2, rats received repeated MMC (7.5, 15 or 30 mg/kg once a day for 10 days) and were examined for residual behavioral effects following treatment. Repeated high (30 mg/kg) dose MMC produced impaired novel object recognition 5 weeks after drug treatment. However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.
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spelling doaj.art-64e0f058b7d54634bd898e7984ee7e5d2022-12-22T03:48:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4547310.1371/journal.pone.0045473Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.Craig P MotbeyEmily KarangesKong M LiShane WilkinsonAdam R WinstockJohn RamsayCallum HicksMichael D KendigNaomi WyattPaul D CallaghanIain S McGregorMephedrone (4-methylmethcathinone, MMC) is a popular recreational drug, yet its potential harms are yet to be fully established. The current study examined the impact of single or repeated MMC exposure on various neurochemical and behavioral measures in rats. In Experiment 1 male adolescent Wistar rats received single or repeated (once a day for 10 days) injections of MMC (30 mg/kg) or the comparator drug methamphetamine (METH, 2.5 mg/kg). Both MMC and METH caused robust hyperactivity in the 1 h following injection although this effect did not tend to sensitize with repeated treatment. Striatal dopamine (DA) levels were increased 1 h following either METH or MMC while striatal and hippocampal serotonin (5-HT) levels were decreased 1 h following MMC but not METH. MMC caused greater increases in 5-HT metabolism and greater reductions in DA metabolism in rats that had been previously exposed to MMC. Autoradiographic analysis showed no signs of neuroinflammation ([(125)I]CLINDE ligand used as a marker for translocator protein (TSPO) expression) with repeated exposure to either MMC or METH. In Experiment 2, rats received repeated MMC (7.5, 15 or 30 mg/kg once a day for 10 days) and were examined for residual behavioral effects following treatment. Repeated high (30 mg/kg) dose MMC produced impaired novel object recognition 5 weeks after drug treatment. However, no residual changes in 5-HT or DA tissue levels were observed at 7 weeks post-treatment. Overall these results show that MMC causes acute but not lasting changes in DA and 5-HT tissue concentrations. MMC can also cause long-term memory impairment. Future studies of cognitive function in MMC users are clearly warranted.http://europepmc.org/articles/PMC3445542?pdf=render
spellingShingle Craig P Motbey
Emily Karanges
Kong M Li
Shane Wilkinson
Adam R Winstock
John Ramsay
Callum Hicks
Michael D Kendig
Naomi Wyatt
Paul D Callaghan
Iain S McGregor
Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
PLoS ONE
title Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
title_full Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
title_fullStr Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
title_full_unstemmed Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
title_short Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
title_sort mephedrone in adolescent rats residual memory impairment and acute but not lasting 5 ht depletion
url http://europepmc.org/articles/PMC3445542?pdf=render
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