Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines

Jeffrey S. Mogil, Pamela Flodman, M. Anne Spence, Wendy F. Sternberg, Benjamin Kest, Bogdan Sadowski, John C. Liebeskind, John Belknap

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Two ongoing selective breeding projects have produced mice that display divergent analgesic responses to morphine. These two projects have selected for similar phenotypes: high and low levorphanol analgesia (HAR/LAR lines; Portland, OR) and high and low swim stress-induced analgesia (HA/LA lines; Jastrzebiec, Poland). Evidence suggests genetic commonalities between mice of the two projects. Using a Mendelian breeding protocol, we have recently found that one or two genetic loci predominantly determine the high morphine analgesia exhibited by HA mice. In the present study we demonstrate that the differential morphine analgesia (5 mg/kg. i.p.) displayed by HAR and LAR mice is similarly oligogenic, predominantly determined by two unlinked loci. A complementation analysis, in which the analgesic responses to morphine of the recessive homozygotes of each project (HAR and HA) were compared to those of their hybrid offspring (HAR x HA), revealed that different genetic loci have been fixed in each project. An intriguing bimodal distribution was observed in the HAR x HA population: Some HAR x HA hybrids displayed greater morphine analgesia than either HAR or HA mice, whereas others displayed minimal analgesia. LAR x LA hybrids displayed less analgesia than either LAR or LA mice. The analgesic responses of HAR x LA and LAR x HA mice were comparable to those of their low-line parents. These findings indicate not only that different loci were responsible for producing high morphine responders in each selection project but that these distinct loci can interact synergistically to produce "superhigh" and "superlow" responders.

Original languageEnglish (US)
Pages (from-to)397-406
Number of pages10
JournalBehavior Genetics
Volume25
Issue number4
DOIs
StatePublished - Jul 1995

Fingerprint

morphine
genetic analysis
analgesics
analgesia
Analgesia
Morphine
genetic techniques and protocols
Analgesics
breeds
mice
loci
Genetic Loci
Levorphanol
selective breeding
Homozygote
Poland
selection methods
homozygosity
project
phenotype

Keywords

  • analgesia
  • complementation
  • genetic segregation
  • levorphanol
  • Opiate
  • pain inhibition
  • selection

ASJC Scopus subject areas

  • Psychology(all)
  • Behavioral Neuroscience
  • Genetics(clinical)
  • Genetics

Cite this

Mogil, J. S., Flodman, P., Spence, M. A., Sternberg, W. F., Kest, B., Sadowski, B., ... Belknap, J. (1995). Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines. Behavior Genetics, 25(4), 397-406. https://doi.org/10.1007/BF02197290

Oligogenic determination of morphine analgesic magnitude : A genetic analysis of selectively bred mouse lines. / Mogil, Jeffrey S.; Flodman, Pamela; Spence, M. Anne; Sternberg, Wendy F.; Kest, Benjamin; Sadowski, Bogdan; Liebeskind, John C.; Belknap, John.

In: Behavior Genetics, Vol. 25, No. 4, 07.1995, p. 397-406.

Research output: Contribution to journalArticle

Mogil, JS, Flodman, P, Spence, MA, Sternberg, WF, Kest, B, Sadowski, B, Liebeskind, JC & Belknap, J 1995, 'Oligogenic determination of morphine analgesic magnitude: A genetic analysis of selectively bred mouse lines', Behavior Genetics, vol. 25, no. 4, pp. 397-406. https://doi.org/10.1007/BF02197290
Mogil, Jeffrey S. ; Flodman, Pamela ; Spence, M. Anne ; Sternberg, Wendy F. ; Kest, Benjamin ; Sadowski, Bogdan ; Liebeskind, John C. ; Belknap, John. / Oligogenic determination of morphine analgesic magnitude : A genetic analysis of selectively bred mouse lines. In: Behavior Genetics. 1995 ; Vol. 25, No. 4. pp. 397-406.
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