Genetic differences in opioids binding sites and in antinociceptice activities of morphine and ethylketocyclazocine

Abstract

The pattern of [ 3H]nx and [ 3H]EKC binding by brain homogenates was different for each of the three studied strains of mice. CXBH was rich in [ 3H]Nx and relatively poor in [ 3H]EKC sites; CXBK poor in the two sites; C 3H rich in the two sites (especially [ 3H]EKC). Using two antinociceptive tests (hot plate: paw lick and D'Amour and Smith's: tail flick) the activities of morphine paralleled the number of [ 3H]Nx sites (CXBH > C 3H ⪢ CXBK) indicating that the number of mu sites is one of the genetic factors of the amplitude of the response to Mo. The same was true for the activities of EKC when the hot plate test was used (C 3H ⪢ CXBH ≅ CXBK) an observation which favours the view of an involvement of kappa sites in the regulation of the paw lick reaction. However, when the tail flick test was used, C 3H still remained much more reactive to EKC than CXBK but CXBH were unexpectedly also very reactive; we tentatively suggest that EKC might then be acting through mu like sites. In this hypothesis mu and kappa sites would be involved in the regulation of paw lick but essentially a mu type site in that of tail flick. Further experimental evidence is needed.