Mu-opiate receptor binding and function in HOT and COLD selected lines of mice

mu-Opiate receptor binding and function were examined in mice selectively bred for sensitivity (COLD) and resistance (HOT) to ethanol-induced hypothermia. These mice also have differential hypothermic sensitivity to mu-opiates. mu-Opiate receptor density was higher in the frontal cortex of HOT mice compared with COLD mice, but was the same in other brain areas. In addition, there were no line differences in Kd values. Basal adenylate cyclase (AC) activity was similar in both lines, as was the response to forskolin (FS) stimulation. Morphine was more effective at inhibiting FS-AC activity in the hypothalamus of HOT mice compared with COLD mice but was equally effective in the frontal and parietal cortex. There were no differences between lines in basal Ca2+, Mg2+, or Ca2+/Mg(2+)-ATPase activity. Further, 30 min after treatment ATPase activities were not altered in ethanol- or levorphanol-treated mice. These results suggests that mu-opiate biochemical pathways, but not ATPase enzyme systems, may be involved in mediating differential hypothermic sensitivity observed in HOT and COLD mice.