Genetic differences in opiate receptor concentration and sensitivity to ethanol's effects.
The hypothesis that genetic differences in opiate receptor concentration are involved in determining the sensitivity to some of the effects of alcohol was studied by comparing the hypothermic and analgesic effects of ethanol in four strains of mice that can be divided into three groups on the basis of their brain opiate receptor concentration: high (CXBH), low (CXBK) and intermediate (C57BL/6By and BALB/cBy). In the first experiment, animals within each strain were injected with either saline or 1.5 g/kg ethanol and their pain sensitivity was assessed 20 min later by the hot-plate test. The same procedure was repeated 10 days later with a higher dose of ethanol (2.5 g/kg). The lower dose produced analgesia only in CXBH mice, whereas the higher dose produced analgesia in CXBH, C57BL/6By and BALB/cBy mice, but had no effect in CXBK mice. In the second experiment, animals within each strain were injected with either saline or naloxone, followed 20 min later by an injection of 3.5 g/kg ethanol. CXBH mice were significantly more hypothermic and CXBK mice were significantly less hypothermic than all other strains. Naloxone attenuated ethanol's hypothermic effect in all strains except CXBK. These results suggest that the hypothermic and analgesic effects of ethanol are at least partly mediated by opiate receptors and are correlated with genetic differences in opiate receptor concentration.
Yirmiya
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Department of Anatomy and Cell Biology, University of California, Los Angeles 90024-1563.
Taylor
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D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D013045:Species Specificity; D013997:Time Factors
D011957:Receptors, Opioid; D009270:Naloxone; D000431:Ethanol