Unique behavioural phenotypes of recombinant-inbred CXBK mice: partial deficiency of sensitivity to mu- and kappa-agonists.
Recombinant-inbred CXBK mice have been used for various studies as putative mu-opioid-receptor deficient mice. However, CXBK mice have never been compared with gene-targeting mice lacking the mu-opioid receptor (muKO) and the K-opioid receptor (kappaKO). Here we report that CXBK mice show distinct behavioural phenotype in opioid-induced analgesia and sedation. Intraperitoneal (i.p.) administration of morphine (3 and 10 mg kg(-1)) induced significantly lower levels of analgesia in CXBK mice than in the control C57BL/6 mice, while higher doses of morphine (30 and 100 mg kg(-1)) induced marked analgesia in CXBK mice. CXBK mice also showed lower analgesia and sedation levels than did C57 mice after i.p. administration of U-50488 (10 and 30 mg kg(-1)). The partial deficiency of sensitivity to morphine and U-50488 of CXBK mice is in sharp contrast to the complete lack of sensitivity to morphine and U-50488 in muKO and kappaKO mice, respectively. Furthermore, CXBK mice showed a lower threshold for nociceptive stimuli when they were not given an opioid, suggesting that CXBK mice could have alterations in the genes related to the nociceptive threshold. These unique behavioural phenotypes of CXBK mice suggest unique genetic alterations in CXBK mice.
Ikeda
K
K
Laboratory for Cellular Information Processing, Brain Science Institute, RIKEN, Wako, Saitama, Japan. ikedak@postman.riken.go.jp
Ichikawa
T
T
Kobayashi
T
T
Kumanishi
T
T
Oike
S
S
Yano
R
R
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000209:etiology; D017288:Pain Threshold; D010641:Phenotype; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics; D011995:Recombination, Genetic; D012680:Sensitivity and Specificity; D013045:Species Specificity
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine