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

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 pA2 of apomorphinehaloperidol 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 Kd of haloperidol binding sites between saline- and morphine-pretreated mice. There was, however, a significant increase in the Bmax 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.