Naloxone's suppression of spontaneous and food-conditioned locomotor activity is diminished in mice lacking either the dopamine D(2) 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 beta-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.
Hayward
Michael D
MD
Vollum Institute L-474, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR 97239, USA. haywarmi@ohsu.edu
Low
Malcolm J
MJ
D000818:Animals; D003214:Conditioning, Classical; D003433:Crosses, Genetic; D004745:Enkephalins / Q000172:deficiency* / Q000235:genetics; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D004745:Enkephalins; D017448:Receptors, Dopamine D2; D009270:Naloxone; D009020:Morphine