MODULATION OF MORPHINE ANTINOCICEPTION BY THE BRAIN-PENETRATING H-2 ANTAGONIST ZOLANTIDINE - DETAILED CHARACTERIZATION IN 5 NOCICEPTIVE TEST SYSTEMS

Because histamine (HA) in the CNS may be a mediator of antinociception , a detailed investigation of the effects of the brain-penetrating H-2 antagonist zolantidine (ZOL) was performed on five nociceptive tests in the presence and absence of morphine (MOR) in rats. ZOL inhibited M OR antinociception on the tail flick test, although a diurnal differen ce (inhibition in the dark cycle much greater than light cycle) was fo und. Similar results were found with the hot plate test, although deta ils of the test procedure were significant. In contrast, ZOL induced o pposing effects on MOR antinociception on two nonthermal tests (jump t est and tail pinch test); ZOL alone induced moderate antinociception o n the former test and mild antinociception on the latter test. Thus, Z OL exerts differential effects on baseline nociception and on MOR anti nociception that vary depending on the nociceptive test employed, the light-dark cycle of the subjects, and the degree of stress associated with the nociceptive testing. These complex effects reveal the heterog eneous nature of opiate-induced modulation of nociception, and show th at ZOL is a powerful tool for studying the relationships between opiat es, HA, and nociceptive mechanisms.