title: Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Psychiatry and Behavioral Science, Charleston Alcohol Research Center, Center for Drug and Alcohol Programs, Charleston, SC, USA. griffinw@musc.edu
authors.forename: William C
authors.initials: WC
authors.lastname: Griffin
authors.forename: Robin W
authors.initials: RW
authors.lastname: McGovern
authors.forename: Guinevere H
authors.initials: GH
authors.lastname: Bell
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Randall
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
authors.forename: Kennerly S
authors.initials: KS
authors.lastname: Patrick
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*
chemical_list: D008774:Methylphenidate; D000431:Ethanol