THE ADENOSINE RECEPTOR ANTAGONIST THEOPHYLLINE INDUCES A MONOAMINE-DEPENDENT INCREASE OF THE ANTICATALEPTIC EFFECTS OF NMDA RECEPTOR ANTAGONISTS

Previous work revealed that adenosine antagonists as theophylline reve rsed neuroleptic-induced catalepsy and potentiated anticataleptic effe cts of dopamine agonists reflecting specific adenosine-dopamine recept or interactions in the central nervous system. We tested whether simil ar functional interactions exist between adenosine receptors and gluta mate receptors of the N-methyl-D-asparte (NMDA) subtype. The present s tudy demonstrates that the anticataleptic effects of the competitive N MDA receptor antagonist CGP37849 and the non-competitive NMDA receptor antagonist dizocilpine can be potentiated by coadministration of a th reshold dose of the adenosine receptor antagonist theophylline (2.5 mg /kg, i.p.) in haloperidol (0.5 mg/kg, i.p.)-pretreated rats. This pote ntiation was elicited only with higher doses of CGP37849 (4 and 8 mg/k g, i.p.) or dizocilpine (0.16 mg/kg, i.p.) in haloperidol (0.5 mg/kg, i.p.), but not in reserpine (5 mg/kg, i.p.) plus alpha-methyl-p-tyrosi ne (100 mg/kg, i.p.)-pretreated animals. Therefore, these synergistic interactions seem to be brought about by indirect monoamine-dependent mechanisms rather than direct functional interrelationships between NM DA and adenosine A(2a) receptors.