title: Differences between the nonselective adenosine receptor antagonists caffeine and theophylline in motor and mood effects: studies using medium to high doses in animal models.
abstract: BACKGROUND
  Caffeine and theophylline are methylxanthines that are broadly consumed, sometimes at high doses, and act as minor psychostimulants. Both are nonselective adenosine antagonists for A1 and A2A receptors, which are colocalized with dopamine D1 and D2 receptors in striatal areas. Adenosine antagonists generally have opposite actions to those of dopamine antagonists. Although the effects of caffeine are widely known, theophylline has been much less well characterized, especially at high doses.
  
  
  METHODS
  Adult male CD1 mice were used to study the effect of a broad range of doses (25.0, 50.0 or 100.0mg/kg) of caffeine and theophylline on measures of spontaneous locomotion and coordination, as well as the pattern of c-Fos immunoreactivity in brain areas rich in adenosine and dopamine receptors. In addition, we evaluated possible anxiety and stress effects of these doses.
  
  
  RESULTS
  Caffeine, at these doses, impaired or suppressed locomotion in several paradigms. However, theophylline was less potent than caffeine at suppressing motor parameters, and even stimulated locomotion. Both drugs induced corticosterone release, however caffeine was more efficacious at intermediate doses. While caffeine showed an anxiogenic profile at all doses, theophylline only did so at the highest dose used (50mg/kg). Only theophylline increased c-Fos immunoreactivity in cortical areas.
  
  
  CONCLUSIONS
  Theophylline has fewer disruptive effects than caffeine on motor parameters and produces less stress and anxiety effects. These results are relevant for understanding the potential side effects of methylxanthines when consumed at high doses.
authors.affiliation: Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: López-Cruz
authors.affiliation: Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Salamone
authors.affiliation: Àrea de Psicobiologia, Campus de Riu Sec, Universitat Jaume I, 12071 Castelló, Spain; Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA. Electronic address: correa@psb.uji.es.
authors.forename: Mercè
authors.initials: M
authors.lastname: Correa
mesh_terms: D000339:Affect / Q000187:drug effects*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine; D013806:Theophylline
keywords: Anxiety; Behavioral activation; Incoordination; Methylxanthine; Prefrontal; Striatum