, Volume 225, Issue 3, pp 613–625

Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice

  • William C. GriffinIII
  • Robin W. McGovern
  • Guinevere H. Bell
  • Patrick K. Randall
  • Lawrence D. Middaugh
  • Kennerly S. Patrick
Original Investigation



Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice.


We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the d- and l-isomers of MPH and the metabolite, ethylphenidate (EPH).


In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1–2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625–1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0–2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased d-MPH and l-EPH without changing l-MPH brain concentrations.


The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain d-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.


Psychostimulant Methylphenidate Ethanol Interoceptive Reinforcement Ataxia Mouse Drug–drug interaction 


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • William C. GriffinIII
    • 1
    • 5
  • Robin W. McGovern
    • 2
  • Guinevere H. Bell
    • 3
  • Patrick K. Randall
    • 1
  • Lawrence D. Middaugh
    • 4
  • Kennerly S. Patrick
    • 3
  1. 1.Department of Psychiatry and Behavioral ScienceCharleston Alcohol Research Center, Center for Drug and Alcohol ProgramsCharlestonUSA
  2. 2.Department of PsychologyWestminster CollegeNew WilmingtonUSA
  3. 3.Department of Pharmaceutical and Biomedical SciencesMedical University of South CarolinaCharlestonUSA
  4. 4.Department of Psychiatry and Behavioral Science and NeurosciencesCharleston Alcohol Research Center, Center for Drug and Alcohol Programs and Medical University of South CarolinaCharlestonUSA
  5. 5.Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, MSC 861Medical University of South CarolinaCharlestonUSA

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