Loss of locomotor sensitisation in response to morphine in D1 receptor deficient mice

Mice lacking D1 receptors were used to study the role of these receptors in morphine-induced antinociception and locomotor sensitisation, In the hot-p late test D1 receptor deficient (-/-) and wild-type (+/+) mice showed simil ar reaction times under basal conditions. A single injection of 1.25 mg;kg and 2.5 mg/kg morphine resulted in a stronger antinociceptive response in D 1 receptor deficient mice than in wild-type animals. Tolerance to the analg esic effect did not develop in both groups of animals when 12.5 mg/kg morph ine was chronically applied twice daily for 13 days. There was no change in t asal locomotor activity between saline-injected wild-type and D1 recepto r deficient mice. After chronic treatment wild-type mice showed a continuou s increase in locomotor activity indicating the development of sensitisatio n. In contrast, a subchronic administration of morphine did not change loco motor activity in mutant mice. The lack of the development of locomotor sen sitisation in D1 deficient mice was associated with reduced levels of immun oreactive mu opioid receptors in dorsal striatal patches as compared to wil d-type mice. In contrast, no change in the distribution of immunoreactive m u receptors could be detected in areas related to pain pathways such as the spinal cord. Taken together, these results suggest an involvement of DI re ceptors in morphine-induced locomotor activity and analgesia.