SEX-DIFFERENCES IN OPIOID ANTINOCICEPTION

Previous studies indicate that mu opioid agonists such as morphine may produce greater antinociception in male than in female rodents. The p resent study was designed to investigate the generality of this findin g across dose, time and type of opioid agonist. In adult female and ma le Sprague-Dawley rats, time-effect curves were obtained for vehicle a nd three doses each of the mu agonists fentanyl and buprenorphine, the kappa agonists (5 alpha,7 alpha 8 lidinyl)-1-oxaspiro-(4,5)dec-8-yl]b enzeneacetamide (U69,593) and bremazocine and the delta agonists [D-Pe n(2),D-Pen(5)]enkephalin (DPDPE) and deltorphin on the 52 degrees C ho t-plate and tail-withdrawal (immersion) assays. There were sex differe nces in the antinociceptive effects of the two kappa agonists and the two delta agonists, but the differences were assay-, dose-and/or time- dependent. Peak effects of U69,593 on tail withdrawal and DPDPE on hot plate tended to occur earlier in females than in males, and bremazoci ne produced greater tail-withdrawal antinociception in females than in males, whereas the highest doses of the two delta opioids produced gr eater hot-plate antinociception in males than in females. These result s contrast with several previous reports showing that male rodents are more sensitive than females to the antinociceptive effects of mu and kappa (but not delta) opioids. These discrepancies may be caused by th e more comprehensive examination of sex differences across dose and ti me used in the present study; sex differences that are dose-or time-de pendent may not be apparent if a single dose or time point is examined . In addition, repeated testing procedures used in the present study m ay produce different results than acute testing procedures would, if f emale and male rats develop opioid tolerance at different rates.