STRESS-DEPENDENT ANTINOCICEPTIVE EFFECTS OF CARBAMAZEPINE - A STUDY IN STRESSED AND NONSTRESSED RATS

1. The present study examined the antinociceptive effects of carbamaze pine on the tail flick test in stressed and nonstressed rats. 2. Carba mazepine produced a bimodal antinociceptive effect in stressed rats, t he first peak appearing 30 min and the second 4 h after injection. Ant inociceptive effect was not observed in nonstressed rats. 3. The secon dary, but not the initial, carbamazepine antinociception in stressed r ats was blocked by naloxone (0.2 mg/kg, i.p.), an opioid receptor anta gonist. 4. Caffeine (5 mg/kg, i.p.), an adenosine A1/A2 receptor antag onist, inhibited the both initial and secondary antinociceptive effect s of carbamazepine in stressed rats. 5. Carbamazepine increased the an tinociceptive effect induced by either i.p. or i.c.v. administration o f N-6-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 s tressed rats may be produced via an activation of the adensosine A1 re ceptors, such as was produced by CHA. The secondary long-lasting antin ociceptive effects of carbamazepine may be mediated by an activation o f opioid systems. 7. Furthermore, the initial activation of the adenos ine A1 receptors by carbamazepine may be a triggering factor for the s ubsequent long-lasting activation of the opioid system, which results in the antinociception effects.