title: Involvement of adenosine A1 receptors in the discriminative-stimulus effects of caffeine in rats.
abstract: BACKGROUND
  Caffeine is a non-selective adenosine receptor antagonist in vitro, but involvement of different adenosine receptor subtypes, particularly adenosine A1 and A 2A receptors, in the central effects of caffeine remains a matter of debate.
  
  
  OBJECTIVE
  Investigate the role of adenosine A1 and A 2A receptors in the discriminative-stimulus effects of caffeine.
  
  
  METHODS
  Rats were trained to discriminate an injection of 30 mg/kg (i.p.) caffeine from saline. The selective A1 receptor antagonist CPT, the selective A 2A receptor antagonist MSX-3 and the non-selective adenosine receptor antagonist DMPX were assessed for their ability to produce caffeine-like discriminative effects. The ability of CPT, MSX-3, the A1 receptor agonist CPA and the A 2A receptor agonist CGS21680 to reduce the discriminative effects of caffeine was also tested. Radioligand binding experiments with membrane preparations from rat striatum and transfected mammalian cell lines were performed to characterize binding affinity profiles of the different adenosine antagonists used in the present study (caffeine, DMPX, CPT and MSX-3) in relation to all known adenosine receptors (A1, A 2A, A 2B, A3).
  
  
  RESULTS
  DMPX and CPT, but not MSX-3, produced significant caffeine-like discriminative effects. MSX-3, but not CPT, markedly reduced the discriminative effects of caffeine and the caffeine-like discriminative effects of CPT. Furthermore, the A1 receptor agonist CPA, but not the A 2A agonist CGS21680, reduced caffeine's discriminative effects.
  
  
  CONCLUSIONS
  Adenosine A1 receptor blockade is involved in the discriminative-stimulus effects of behaviorally relevant doses of caffeine; A 2A receptor blockade does not play a central role in caffeine's discriminative effects and counteracts the A1 receptor-mediated discriminative-stimulus effects of caffeine.
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, NIDA-IRP, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Katerina
authors.initials: K
authors.lastname: Antoniou
authors.forename: Davide
authors.initials: D
authors.lastname: Quarta
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Justinova
authors.forename: Jörg
authors.initials: J
authors.lastname: Hockemeyer
authors.forename: Lara A
authors.initials: LA
authors.lastname: Pappas
authors.forename: Pavan N
authors.initials: PN
authors.lastname: Segal
authors.forename: Carrie
authors.initials: C
authors.lastname: Wertheim
authors.forename: Christa E
authors.initials: CE
authors.lastname: Müller
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000737:chemistry / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D043682:Receptor, Adenosine A1 / Q000502:physiology*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D002110:Caffeine