Original Investigation

Psychopharmacology

, Volume 225, Issue 3, pp 613-625

First online:

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

  • William C. GriffinIIIAffiliated withDepartment of Psychiatry and Behavioral Science, Charleston Alcohol Research Center, Center for Drug and Alcohol ProgramsCharleston Alcohol Research Center, Center for Drug and Alcohol Programs, MSC 861, Medical University of South Carolina Email author 
  • , Robin W. McGovernAffiliated withDepartment of Psychology, Westminster College
  • , Guinevere H. BellAffiliated withDepartment of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina
  • , Patrick K. RandallAffiliated withDepartment of Psychiatry and Behavioral Science, Charleston Alcohol Research Center, Center for Drug and Alcohol Programs
  • , Lawrence D. MiddaughAffiliated withDepartment of Psychiatry and Behavioral Science and Neurosciences, Charleston Alcohol Research Center, Center for Drug and Alcohol Programs and Medical University of South Carolina
  • , Kennerly S. PatrickAffiliated withDepartment of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina

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Abstract

Introduction

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.

Methods

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).

Results

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.

Conclusions

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.

Keywords

Psychostimulant Methylphenidate Ethanol Interoceptive Reinforcement Ataxia Mouse Drug–drug interaction