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

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.

journal_name

Behav Genet

journal_title

Behavior genetics

authors

Mogil JS,Flodman P,Spence MA,Sternberg WF,Kest B,Sadowski B,Liebeskind JC,Belknap JK

doi

10.1007/BF02197290

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

397-406

issue

4

eissn

0001-8244

issn

1573-3297

journal_volume

25

pub_type

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