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-plate test D1 receptor deficient (-/-) and wild-type (+/+) mice showed similar 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 D1 receptor deficient mice than in wild-type animals. Tolerance to the analgesic effect did not develop in both groups of animals when 12.5 mg/kg morphine was chronically applied twice daily for 13 days. There was no change in basal locomotor activity between saline-injected wild-type and D1 receptor deficient mice. After chronic treatment wild-type mice showed a continuous increase in locomotor activity, indicating the development of sensitisation. In contrast, a subchronic administration of morphine did not change locomotor activity in mutant mice. The lack of the development of locomotor sensitisation in D1 deficient mice was associated with reduced levels of immunoreactive mu opioid receptors in dorsal striatal patches as compared to wild-type mice. In contrast, no change in the distribution of immunoreactive mu receptors could be detected in areas related to pain pathways such as the spinal cord. Taken together, these results suggest an involvement of D1 receptors in morphine-induced locomotor activity and analgesia.
Becker
A
A
Otto-von-Guericke Universität, Medizinische Fakultät, Institut für Pharmakologie und Toxikologie, Magdeburg, Germany. axel.becker@medizin.uni-magdeburg.de
Grecksch
G
G
Kraus
J
J
Peters
B
B
Schroeder
H
H
Schulz
S
S
Höllt
V
V
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects*; D020671:Posterior Horn Cells / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
D000701:Analgesics, Opioid; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D009020:Morphine