Increased sensitivity to dopamine agonists following a single dose of morphine or levorphanol in mice

Abstract

Acute administration of an opiate has been suggested to result in the development of supersensitive dopamine receptors. This hypothesis was tested in mice by determining the effect of a single administration of morphine or levorphanol on dopamine agonist-induced stereotypic behaviors and [3H]spiroperidol binding. Administration of morphine (1.0 mg/kg s.c.), which itself had no significant effect on spontaneous locomotor activity 3 h following administration, significantly potentiated locomotor activity induced by 1.5 or 4.5 mg/kg of apomorphine (i.p.) administered 3 h later. Morphine (10 mg/kg, s.c.) or levorphanol (0.2 and 2.0 mg/kg, s.c.), but not dextrorphan (up to 20 mg/kg, s.c.), enhanced climbing behavior induced by apomorphine (i.p.) or (-)-N-n-propylnorapomorphine (i.p.; NPA) administered 3 h later. An increase in whole brain and striatal [3H]spiroperidol binding sites was found 3 h after administration of 10 mg/kg of morphine. Concurrent administration of 5 mEq/kg of LiCl (i.p.) or 5 mg/kg of naloxone (i.p.; administered twice) attenuated both the potentiation of the climbing behavior induced by the two dopamine agonists and the increase in [3H]spiroperidol binding sites. These results suggest that a single administration of an opiate can induce the development of supersensitive dopamine receptors that is mediated by an interaction at opioid receptors.