Chronic treatment with naltrexone enhances morphine-stimulated dopamine neurotransmission: neurochemical and behavioral evidence.

Rats were implanted for 10 days with a slow-release pellet of naltrexone or were given sham surgery. At one of various different intervals during or after implantation of the pellet, the synthesis of dopamine (DA) was assessed in the nigrostriatal and mesolimbic systems. The results indicated that naltrexone alone was without effect on the synthesis of DA. However, one day after removal of the pellet, naltrexone-treated animals displayed an enhanced response to the DA-stimulatory action of morphine (15 mg/kg) in both the nigrostriatal and mesolimbic systems. This change was accompanied by an increase in specific binding of the mu-specific radioligand [3H]DAGO in whole brain and by an increase in the depressant action of morphine on locomotor activity. In contrast, at 10 days after removal of the pellet, naltrexone was without effect on morphine-induced changes in the synthesis of DA and locomotor activity, thus indicating that the supersensitivity to morphine was transient. These results support the idea that opioids modulate DAergic neurotransmission in the nigrostriatal and mesolimbic pathways and that this modulatory role may underlie opiate-induced changes in locomotor behavior.