TY - JOUR
T1 - Genetic determinants of morphine activity and thermal responses in 15 inbred mouse strains
AU - Belknap, J. K.
AU - Riggan, J.
AU - Cross, S.
AU - Young, E. R.
AU - Gallaher, E. J.
AU - Crabbe, J. C.
N1 - Funding Information:
These studies were supported by three Merit Review grants from the Department of Veterans Affairs and by NIH Grants DA05228 and DA10913.
PY - 1998/2
Y1 - 1998/2
N2 - Mice from 15 standard inbred strains were tested for sensitivity to two effects of acute morphine administration, open-field activity, and body temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, IF. Large strain differences were consistently observed, indicating a substantial degree of genetic determination of these traits. For morphine-induced activity, some strains were markedly insensitive to all doses (e.g., C3H/He, CE), while others showed increases and some decreases at the same morphine dose. For thermal responses, one strain was insensitive to all doses employed (C3H/He), while others showed marked hypothermia and some hyperthermia at the same dose. Although strains differed in brain morphine concentrations at time of behavioral testing, pharmacokinetic differences were unrelated to both measures of morphine sensitivity. Correlations among strain means (estimates of genetic correlations) were rather high across doses within each measure, indicating that strain differences to a given effect of morphine were rather stable across doses. This suggests substantial commonality in genetically mediated mechanisms across the dose range used for activity, and also for thermal responses. In contrast, genetic correlations between activity and thermal responses were not significant at any dose, indicating that these two traits are largely genetically independent.
AB - Mice from 15 standard inbred strains were tested for sensitivity to two effects of acute morphine administration, open-field activity, and body temperature changes, at doses of 0, 4, 8, 16, and 32 mg/kg, IF. Large strain differences were consistently observed, indicating a substantial degree of genetic determination of these traits. For morphine-induced activity, some strains were markedly insensitive to all doses (e.g., C3H/He, CE), while others showed increases and some decreases at the same morphine dose. For thermal responses, one strain was insensitive to all doses employed (C3H/He), while others showed marked hypothermia and some hyperthermia at the same dose. Although strains differed in brain morphine concentrations at time of behavioral testing, pharmacokinetic differences were unrelated to both measures of morphine sensitivity. Correlations among strain means (estimates of genetic correlations) were rather high across doses within each measure, indicating that strain differences to a given effect of morphine were rather stable across doses. This suggests substantial commonality in genetically mediated mechanisms across the dose range used for activity, and also for thermal responses. In contrast, genetic correlations between activity and thermal responses were not significant at any dose, indicating that these two traits are largely genetically independent.
KW - Genetics
KW - Hyperthermia
KW - Hypothermia
KW - Inbred mouse
KW - Locomotor activity
KW - Morphine
KW - Thermoregulation
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U2 - 10.1016/S0091-3057(97)00421-8
DO - 10.1016/S0091-3057(97)00421-8
M3 - Article
C2 - 9476981
AN - SCOPUS:0032005723
SN - 0091-3057
VL - 59
SP - 353
EP - 360
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -