Effects of drugs active at adenosine receptors on stress-induced analgesia in mice.

Mice were stressed by swimming for 3 min in water at 20 degrees C and antinociception was assessed by the tail-flick test. The stress-induced antinociception was potentiated by intraperitoneal administration of different doses of theophylline. The effect of the drug was dose-dependent. 5'-N-Ethylcarboxamidoadenosine administration also increased the stress response dose-dependently. N6-Phenyl-isopropyladenosine decreased the antinociception induced by swim-stress as well as after stress plus theophylline. Administration of dipyridamole caused a decrease of antinociception induced by stress or stress plus theophylline. It may be concluded that activation of A2 adenosine receptors increased whereas activation of A1 adenosine sites decreased the stress-induced antinociception. The responses of A2 or A1 activation may be irrelevant to changes in cAMP levels. Because the adenosine agonists and antagonists employed were not selective at the receptor level, other possibilities are not excluded.