Different influences of adenosine receptor agonists and antagonists on morphine antinociception in mice.

1. Subcutaneous (s.c.) administration of morphine to mice induced a dose-dependent antinociception. 2. Pretreatment of animals with adenosine receptor antagonists NECA (5'-N-ethylcarboxamide-adenosine) and L-PIA (N6-phenylisopropyladenosine) potentiated, while adenosine agonist CHA (N6-cyclohexyladenosine) decreased the morphine response. 3. Adenosine antagonist theophylline decreased, but adenosine receptor antagonist 8-PT (8-phenyltheophylline) increased the antinociception effect of morphine. Inhibitory effect of CHA on morphine antinociception was also reversed by 8-PT pretreatment. 4. NECA or L-PIA induced a high degree of antinociceptive effect in animals pretreated with 8-PT. 5. Dipyridamole pretreatment did not alter the effect of morphine. 6. It is concluded that A-1 and/or A-2 adenosine receptors are involved in morphine antinociception and the adenosine mechanism(s) may exert a modulatory role in this respect.