Opioid receptor agonists and antagonists alter GBR12909-induced turning in the rat

We extended observations on cocaine-induced turning and its interactions with mu-opioid receptor agonists in nigrally-lesioned rats to GBR12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenyl-propyl]-piperazine) , a selective dopamine reuptake inhibitor. GBR12909 produced turning that was potentiated by the mu-opioid receptor agonists morphine and methadone. The effects of these opioids were blocked by the general opioid receptor antagonist naloxone, which did not affect the action of GBR12909. The reuptake inhibitors nisoxetine (norepinephrine) and fluoxetine (serotonin) did not produce turning alone or in combination with morphine. Antagonists selective for each opioid receptor subtype did not alter GBR12909-induced turning. However, naltrexone, another general opioid receptor antagonist, potentiated turning induced by GBR12909. This was blocked by naloxone, suggesting that naltrexone has opioid receptor agonist actions, in contrast to naloxone. These results indicate that cocaine-induced turning and its potentiation by mu-opioid receptor agonists are dependent upon the inhibition of dopamine reuptake.