Peripheral Antinociception Induced by Aripiprazole Is Mediated by the Opioid System

Background. Aripiprazole is an antipsychotic drug used to treat schizophrenia and related disorders. Our previous study showed that this compound also induces antinociceptive effects. The present study aimed to assess the participation of the opioid system in this effect. Methods. Male Swiss mice were submitted to paw pressure test and hyperalgesia was induced by intraplantar injection of prostaglandin E-2 (PGE(2), 2 mu g). Aripiprazole was injected 10 min before the measurement. Naloxone, clocinnamox, naltrindole, nor-binaltorphimine, and bestatin were given 30 min before aripiprazole. Nociceptive thresholds were measured in the 3rd hour after PGE(2) injection. Results. Aripiprazole (100 mu g/paw) injected locally into the right hind paw induced an antinociceptive effect that was blocked by naloxone (50 mu g/paw), a nonselective opioid receptor antagonist. The role of mu-, delta-, and kappa- opioid receptors was investigated using the selective antagonists, clocinnamox (40 mu g/paw), naltrindole (15, 30, and 60 mu g/paw), and nor-binaltorphimine (200 mu g/paw), respectively. The data indicated that only the delta-opioid receptor antagonist inhibited the peripheral antinociception induced by aripiprazole. Bestatin (400 mu g), an aminopeptidase-N inhibitor, significantly enhanced low-dose (25 mu g/paw) aripiprazole-induced peripheral antinociception. Conclusion. The results suggest the participation of the opioid system via delta-opioid receptor in the peripheral antinociceptive effect induced by aripiprazole.