title: Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion.
abstract: 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.
authors.affiliation: School of Psychology, University of Sydney, New South Wales, Australia.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Motbey
authors.forename: Emily
authors.initials: E
authors.lastname: Karanges
authors.forename: Kong M
authors.initials: KM
authors.lastname: Li
authors.forename: Shane
authors.initials: S
authors.lastname: Wilkinson
authors.forename: Adam R
authors.initials: AR
authors.lastname: Winstock
authors.forename: John
authors.initials: J
authors.lastname: Ramsay
authors.forename: Callum
authors.initials: C
authors.lastname: Hicks
authors.forename: Michael D
authors.initials: MD
authors.lastname: Kendig
authors.forename: Naomi
authors.initials: N
authors.lastname: Wyatt
authors.forename: Paul D
authors.initials: PD
authors.lastname: Callaghan
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D015198:Designer Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000378:metabolism*; D057567:Memory, Long-Term / Q000187:drug effects; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015198:Designer Drugs; D012701:Serotonin; D008694:Methamphetamine; C548233:mephedrone; D004298:Dopamine