Further evidence that a single dose of an opiate can increase dopamine receptor sensitivity in mice

Abstract

Previous findings in our laboratory indicated that a single administration of morphine or levorphanol to mice could induce the development of supersensitive dopamine receptors. To further study this phenomenon, the ability of haloperidol to inhibit dopamine agonist-induced climbing was determined in mice 3 h following morphine (10 mg/kg i.p.) or levorphanol (2.0 mg/kg i.p.) pretreatment. The dose of haloperidol required to inhibit climbing behavior induced by 2.4 mg/kg (i.p.) of apomorphine or (−)N-n-propylnorapomorphine was increased significantly in the opiate-pretreated mice. Morphine pretreatment did not significantly affect the apparent pA 2 of apomorphine-haloperidol for climbing behavior suggesting that the affinity of the dopamine receptor was not altered. This observation was supported by a lack of difference in the K d of haloperidol binding sites between saline- and morphine-pretreated mice. There was, however, a significant increase in the B max in the morphine-pretreated animals. This increase was blocked when 5 mEq/kg of lithium (i.p.) or 5 mg/kg naloxone (i.p., administered twice) was administered concurrently with the morphine. Concurrent lithium or naloxone administration also attenuated the morphine-induced increase in dose of haloperidol required to inhibit dopamine agonist-induced climbing behavior. These results suggest that a single administration of an opiate can cause the development of dopamine receptor supersensitivity which is due to an increase in dopamine receptor density.