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Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion
Craig P Motbey1, Emily Karanges, Kong M Li
1School of Psychology, University of Sydney, New South Wales, Australia.
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.
Insights
Mephedrone (MMC) causes short-term hyperactivity and alters dopamine and serotonin levels. While not causing lasting neurochemical changes, repeated MMC exposure impairs long-term memory in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Mephedrone (4-methylmethcathinone, MMC) is a widely used recreational stimulant.
- The long-term neurochemical and behavioral harms of MMC are not fully understood.
Purpose of the Study:
- To investigate the neurochemical and behavioral effects of single and repeated MMC exposure in rats.
- To assess potential neuroinflammation and residual cognitive deficits following MMC treatment.
Main Methods:
- Rats received single or repeated injections of MMC (30 mg/kg) or methamphetamine (METH).
- Neurochemical analyses (dopamine, serotonin) and behavioral tests (hyperactivity, novel object recognition) were performed.
- Autoradiography was used to detect neuroinflammation markers.
Main Results:
- Both MMC and METH induced acute hyperactivity.
- MMC acutely decreased striatal and hippocampal serotonin (5-HT) and increased dopamine (DA) levels.
- Repeated high-dose MMC impaired novel object recognition memory 5 weeks post-treatment, but no lasting changes in DA or 5-HT tissue levels were observed.
- No neuroinflammation was detected with repeated MMC or METH exposure.
Conclusions:
- MMC causes acute neurochemical alterations but not lasting changes in dopamine and serotonin concentrations.
- Long-term cognitive impairment, specifically in memory, can result from repeated high-dose MMC exposure.
- Further research into the cognitive effects of MMC use is warranted.