Τίτλος:
Involvement of adenosine A1 receptors in the discriminative-stimulus effects of caffeine in rats
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Rationale: Caffeine is a non-selective adenosine receptor antagonist in vitro, but involvement of different adenosine receptor subtypes, particularly adenosine A1 and A2A receptors, in the central effects of caffeine remains a matter of debate. Objective: Investigate the role of adenosine A1 and A2A 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 A2A 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 A2A 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, A2A, A2B, 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 A2A 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; A2A receptor blockade does not play a central role in caffeine's discriminative effects and counteracts the A1 receptor-mediated discriminative-stimulus effects of caffeine. © Springer-Verlag 2005.
Συγγραφείς:
Solinas, M.
Ferré, S.
Antoniou, K.
Quarta, D.
Justinova, Z.
Hockemeyer, J.
Pappas, L.A.
Segal, P.N.
Wertheim, C.
Müller, C.E.
Goldberg, S.R.
Περιοδικό:
Psychopharmacology Bulletin
Λέξεις-κλειδιά:
2 [4 (2 carboxyethyl)phenethylamino]adenosine 5' (n ethylcarboxamide); 3,7 dimethyl 1 propargylxanthine; 6 n cyclopentyladenosine; 8 cyclopentyltheophylline; adenosine 2b receptor; adenosine A1 receptor; adenosine A1 receptor agonist; adenosine A1 receptor antagonist; adenosine A2a receptor; adenosine A2a receptor agonist; adenosine A2a receptor antagonist; adenosine A3 receptor; adenosine receptor; adenosine receptor blocking agent; caffeine; methamphetamine; msx 3; phosphoric acid mono[3 [8 [2 (3 methoxyphenyl)vinyl] 7 methyl 2,6 dioxo 1 prop 2 ynyl 1,2,6,7 tetrahydropurin 3 yl]propyl]ester disodium; radioligand; rolipram; sodium chloride; unclassified drug; caffeine, animal experiment; article; binding affinity; cell line; controlled study; corpus striatum; drug effect; drug selectivity; experiment; genetic transfection; injection; male; mammal cell; membrane; nonhuman; perceptive discrimination; priority journal; protein analysis; protein function; rat; stimulus; training; animal; brain; chemistry; comparative study; discrimination learning; dose response; drug antagonism; human; physiology; reaction time; Sprague Dawley rat, Animals; Brain; Caffeine; Discrimination Learning; Dose-Response Relationship, Drug; Humans; Male; Rats; Rats, Sprague-Dawley; Reaction Time; Receptor, Adenosine A1
DOI:
10.1007/s00213-004-2081-6
