Stereospecific potentiation of opiate analgesia by cocaine: predominant role of noradrenaline.

Cocaine hydrochloride (50 mg) pellets implanted subcutaneously in male Wistar rats potentiated the analgesia of morphine, levorphanol, methadone and buprenorphine as measured by the tail-withdrawal test. Potentiated opiate analgesia was abolished by naloxone and further enhanced by desipramine and phenoxybenzamine. Yohimbine, alpha-methyl p-tyrosine, haloperidol, zimelidine, methysergide, p-chlorophenylalanine produced no significant effect on potentiated opiate analgesia. Pseudo-cocaine (dextro-cocaine), which is several-fold less potent than cocaine as an inhibitor of noradrenaline and dopamine reuptake in the CNS, had no significant effect on opiate analgesia. Analgesia produced by low doses of baclofen, a GABA agonist, was also not potentiated by cocaine. This study suggests a predominant role for noradrenaline in the stereospecific potentiation of opiate analgesia by cocaine.