Abstract
Previous studies have shown that the dopamine (DA) uptake blocker methylphenidate, a psychostimulant widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), prevents the neurotoxic effects of the highly abused DA releaser methamphetamine. However, there is a lack of information about the pharmacological interactions of these two drugs at the behavioral level. When systemically administered within an interval of 2 h, previous administration of methylphenidate (10 mg/kg, intraperitoneal (i.p.)) did not modify locomotor activation induced by methamphetamine. On the other hand, previous administration of methamphetamine (1 mg/kg, i.p.) markedly potentiated methylphenidate-induced motor activation. With in vivo microdialysis experiments, methamphetamine and methylphenidate were found to increase DA extracellular levels in the nucleus accumbens (NAs). Methamphetamine, but not methylphenidate, significantly increased the extracellular levels of serotonin (5-HT) in the NAs. Methamphetamine-induced 5-HT release remained significantly elevated for more than 2 h after its administration, suggesting that the increased 5-HT could be responsible for the potentiation of methylphenidate-induced locomotor activation. In fact, previous administration of the 5-HT uptake blocker fluoxetine (10 mg/kg, i.p.) also potentiated the motor activation induced by methylphenidate. A selective 5-HT1B receptor antagonist (GR 55562; 1 mg/kg), but not a 5-HT2 receptor antagonist (ritanserin; 2 mg/kg, i.p.), counteracted the effects of methamphetamine and fluoxetine on the motor activation induced by methylphenidate. Furthermore, a 5-HT1B receptor agonist (CP 94253; 1–10 mg/kg, i.p.) strongly and dose-dependently potentiated methylphenidate-induced locomotor activation. The 5-HT1B receptor-mediated modulation of methylphenidate-induced locomotor activation in rat could have implications for the treatment of ADHD.
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Work supported by National Institute on Drug Abuse intramural research funds.
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The author(s) declare that, except for income received from my primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.
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Borycz, J., Zapata, A., Quiroz, C. et al. 5-HT1B Receptor-Mediated Serotoninergic Modulation of Methylphenidate-Induced Locomotor Activation in Rats. Neuropsychopharmacol 33, 619–626 (2008). https://doi.org/10.1038/sj.npp.1301445
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DOI: https://doi.org/10.1038/sj.npp.1301445
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