Effect of strain and sex on mu opioid receptor-mediated G-protein activation in rat brain.
Strain and sex differences in mu opioid-mediated antinociception have been reported in rodents. The present studies evaluated mu opioid receptor-mediated G-protein activation in Lewis and Fischer 344 (F344) male and female rats using agonist-stimulated [35S]GTPgammaS binding. Compared to Lewis rats, F344 rats exhibited a 35% higher level of net DAMGO-stimulated [35S]GTPgammaS binding in striatum. Basal [35S]GTPgammaS binding was approximately 30% lower in thalamus of Lewis than F344 rats. Female Lewis rats also exhibited slightly ( approximately 15%) lower basal [35S]GTPgammaS binding in cingulate cortex relative to F344 rats of either sex. The relative efficacies of the mu partial agonists, morphine and buprenorphine, were also examined. Buprenorphine exhibited approximately 40% lower relative efficacy in the periaqueductal gray in Lewis compared to F344 rats, but no other relative efficacy differences were found between strains or sexes. Moreover, regional differences in the relative efficacy of buprenorphine were also detected in Lewis but not F344 rats. In contrast to these results, the only difference found between sexes was the 13% lower basal [35S]GTPgammaS binding in the cingulate cortex of female compared to male Lewis rats. These results suggest that differences in mu opioid receptor-mediated G-protein activation may contribute to strain differences in opioid antinociception, whereas sex differences may result predominantly from other mechanisms.
Selley
Dana E
DE
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Institute for Drug and Alcohol Studies, Virginia Commonwealth University, P.O. Box 980524, 1112 East Clay St., Richmond, VA 23298, USA. deselley@hsc.vcu.edu
Herbert
J Taylor
JT
Morgan
Drake
D
Cook
Charles D
CD
Picker
Mitchell J
MJ
Sim-Selley
Laura J
LJ
D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002047:Buprenorphine / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D009020:Morphine / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012727:Sex Characteristics; D013045:Species Specificity; D013460:Sulfur Isotopes / Q000378:metabolism
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D013460:Sulfur Isotopes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002047:Buprenorphine; D009020:Morphine; D019204:GTP-Binding Proteins