IMPORTANCE OF HISTAMINE H-2 RECEPTORS IN RESTRAINT-MORPHINE INTERACTIONS

The effects of the brain-penetrating H-2 antagonist zolantidine (ZOL, 3 mg/kg, s.c.) were studied on morphine (MOR, 4 mg/kg, s.c.) antinocic eption (tail flick test) in the presence and absence of previous restr aint stress. Animals were handled for 3 days (to reduce handling stres s), restrained for 1 hr or handled on day 4, and tested 24 hrs later. As found previously, restraint enhanced the intensity and duration of MOR antinociception. ZOL potentiated MOR antinociception in handled, n on-restrained animals, but inhibited MOR action in restrained animals. In contrast, ZOL had no effects on nociceptive responses in either ha ndled or stressed subjects in the absence of MOR. The data suggest tha t, in the absence of restraint, brain HA acts at the H-2 receptor to i nhibit MOR antinociception. In contrast, when an animal has been previ ously restrained, HA enhances MOR antinociception. Thus, brain HA appe ars to mediate the restraint-induced potentiation of MOR antinocicepti on. Taken with previous results, the present findings suggest that in the presence of MOR, brain HA can provide bidirectional modulation of nociception. The direction of the modulation seems to depend upon the stress experience of the animal.