Modification of the development of acute opiate tolerance by increased dopamine receptor sensitivity

Earlier studies have suggested that the acute administration of an opiate can result in the development of supersensitive dopamine receptors. The present study was undertaken to determine whether the supersensitive dopamine receptors can modify the development of opiate tolerance and dependence. Administration of morphine (100 mg/kg s.c.) 6 or 24 hr before apomorphine (i.p.) potentiated apomorphine-induced climbing behavior in mice. Administration of levorphanol (12 mg/kg s.c.) 3 or 6 hr, but not 24 hr, before apomorphine also potentiated apomorphine-induced climbing behavior. Coadministration of 5 mEq/kg of LiCl with morphine or levorphanol attenuated the increased sensitivity developed to apomorphine after either opiate. Acute tolerance and dependence was induced by administration of 100 mg/kg of morphine or 12 mg/kg of levorphanol. Lithium enhanced the development of acute tolerance when coadministered with morphine 3, 6 or 24 hr before test doses of morphine, or with levorphanol 3 hr before test doses of levorphanol. Administration of apomorphine 5 min before naloxone significantly decreased the naloxone ED50 for inducing withdrawal jumping in mice that had been pretreated with morphine or levorphanol. Although coadministration of lithium with morphine or levorphanol had no significant effect on naloxone-induced withdrawal jumping, it attenuated the ability of apomorphine to decrease naloxone ED50. Morphine (100 mg/kg s.c.) increased the number of whole brain [3H]spiroperidol binding sites 3 and 6 hr after administration of morphine. This increase was no longer present 24 hr after morphine administration. Levorphanol (12 mg/kg s.c.) also increased the number of binding sites 3 hr after administration. Coadministration of lithium with morphine attenuated the increase in [3H]spiroperidol binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)