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Enhanced responses to opiates produced by a single gene substitution in the mouse
Abstract:
Adult male mice of the C57Bl/6J strain, or mice differing at a single locus from the above, pallid mice (C57Bl/6J-pa), were treated with morphine or vehicle and two responses associated with opiate receptor stimulation were examined. In comparison with vehicle treatment, morphine produced stereotyped running and reduced core temperature in the parent C57Bl/6J line. These responses were significantly enhanced in the coisogenic pallid line. Thus, a single gene may enhance normal sensitivity to opiates. This suggests the existence of discrete and identified biochemical influences upon sensitivity to opiates through genetic means, and offers a novel model of naturally occurring permanently altered opiate sensitivity.
Insights
A single gene significantly enhances morphine sensitivity in mice, increasing stereotyped running and reducing core body temperature. This discovery offers a novel genetic model for altered opiate sensitivity.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Opiate receptor stimulation influences various physiological responses.
- Genetic factors are known to modulate drug sensitivity.
- Understanding genetic influences on opiate sensitivity can reveal novel therapeutic targets.
Purpose of the Study:
- To investigate the impact of a single gene on opiate-induced responses in mice.
- To establish a genetic model for naturally occurring alterations in opiate sensitivity.
- To explore the biochemical influences on sensitivity to opiates.
Main Methods:
- Adult male C57Bl/6J mice and coisogenic pallid mice (C57Bl/6J-pa) were used.
- Mice were treated with morphine or a vehicle control.
- Stereotyped running behavior and core body temperature were measured as indicators of opiate receptor stimulation.
Main Results:
- Morphine induced stereotyped running and reduced core temperature in C57Bl/6J mice.
- These morphine-induced responses were significantly enhanced in the pallid mouse line.
- A single gene locus was identified as influencing heightened sensitivity to opiates.
Conclusions:
- A single gene can significantly enhance normal sensitivity to opiates.
- This study suggests discrete biochemical influences on opiate sensitivity mediated by genetic factors.
- The pallid mouse line provides a novel model for studying naturally occurring, permanent alterations in opiate sensitivity.