Naloxone's suppression of spontaneous and food-conditioned locomotor activity is diminished in mice lacking either the dopamine D2 receptor or enkephalin

Mice lacking the D₂ dopamine receptor (D₂^−/−) and congenic to the C57BL/6J background were tested for opioid-mediated locomotor activity to examine the involvement of the D₂ dopamine receptor in opioid pharmacology. Morphine-stimulated locomotor activity did not significantly differ between the two genotypes. The opioid antagonist naloxone dose-dependently decreased spontaneous motor activity in wild-type mice but was without significant effect in D₂^−/− mice. The magnitude of food-conditioned increases in locomotor activity in wild-type mice and D₂^−/− mice was similar but naloxone did not decrease conditioned motor activity in D₂^−/− mice. Spontaneous locomotor activity of mice lacking the endogenous opioids β-endorphin and/or enkephalin was also tested and we found that naloxone did not reduce activity in mice specifically lacking enkephalin. We suggest that the D₂ dopamine receptor is necessary for modulation of spontaneous locomotor activity stimulated by the endogenous opioid enkephalin.