Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats

Morphine tolerant/dependent rats were tested for their sensitivity to putative neurotransmitters or other receptor agonists injected intracerebroventricularly (i.c.v.) during naloxone-precipitated withdrawal. Dopamine, apomorphine, clonidine and serotonin were found to reinitiate withdrawal jumping behaviour when injected 30 min after naloxone. Dopamine and apomorphine also reinitiated jumping, but of a lesser intensity, when injected 3 h after naloxone-precipitated withdrawal. I.c.v. injection of acetylcholine or prostaglandin E1 failed to reinitiate withdrawal jumping. In addition, all the above substances failed to induce jumping behaviour in naive rats or in morphine tolerant/dependent rats before naloxone-precipitated withdrawal. Morphine tolerance and dependence therefore appears to be associated with changes in the sensitivity of the CNS to putative neurotransmitter substances. These changes are best demonstrated during the sudden termination of opiate action that is caused by administration of naloxone.