Naltrexone induces down- and upregulation of delta opioid receptors in rat brain regions.

Opioid antagonists such as naltrexone, naloxone, and ICI174864 induce a transient downregulation of delta opioid receptors prior to upregulation in NG108-15 cells. Here we show that naltrexone can also elicit a transient downregulation of delta 2 opioid receptors preceding upregulation in brain. A 1 h treatment of rats with naltrexone (IP, 10 mg/kg) resulted in lowered 3H-[D-Ser2,L-Leu5]enkephalyl-Thr Bmax values in hindbrain, but not in striatum, hippocampus, or cortex. The decrease in hindbrain delta 2 receptor density was not accompanied by changes in Kd values, indicating that downregulation rather than receptor blockade occurred. Longer naltrexone treatment (48 h), caused twofold upregulation of delta opioid binding in all four regions. These data suggest that the process of upregulation of delta opioid receptors by antagonists in vivo can entail an initial, transient downregulation.