Stress-dependent antinociceptive effects of carbamazepine: a study in stressed and nonstressed rats

1. The present study examined the antinociceptive effects of carbamazepine on the tail flick test in stressed and nonstressed rats. 2. Carbamazepine produced a bimodal antinociceptive effect in stressed rats, the first peak appearing 30 min and the second 4 h after injection. Antinociceptive effect was not observed in nonstressed rats. 3. The secondary, but not the initial, carbamazepine antinociception in stressed rats was blocked by naloxone (0.2 mg/kg, i.p.), an opioid receptor antagonist. 4. Caffeine (5 mg/kg, i.p.), an adenosine A1/A2 receptor antagonist, inhibited the both initial and secondary antinociceptive effects of carbamazepine in stressed rats. 5. Carbamazepine increased the antinociceptive effect induced by either i.p. or i.c.v. administration of N6-cyclohexyl adenosine (CHA), an adenosine A1 receptor agonist, in stressed rats, but decreased it in nonstressed rats. 6. These results suggest that the initial antinociceptive effect of carbamazepine in stressed rats may be produced via an activation of the adenosine A1 receptors, such as was produced by CHA. The secondary long-lasting antinociceptive effects of carbamazepine may be mediated by an activation of opioid systems. 7. Furthermore, the initial activation of the adenosine A1 receptors by carbamazepine may be a triggering factor for the subsequent long-lasting activation of the opioid system, which results in the antinociception effects.