The first objective of the proposed work is to continue bidirectional selective breeding to produce three lines of mice which differ maximally from one another in their genetically-based sensitivity to analgesic (antinociceptive) effects of opiate drugs (narcotic analgesics). To this end, three lines will be maintained: one will be selectively bred in the direction of a high antinociceptive response, another in the direction of a low antinociceptive response, and the third will be a (nonselected) control line. Selection will be based on latencies on the hot plate assay in response to levorphanol, morphine-like opioid agonist. The second objective is to conduct studies to determine the mechanisms which account for the selection line differences, and a search made for other effects of opioids which may share common mechanisms with the antinociceptive response. The third objective is to screen a considerable number of novel analgesics using these selection lines to determine the extent to which their mechanisms of action overlap with levorphanol or morphine. These animals should be a valuable resource for research concerning the actions of analgesic drugs and mechanisms of pain in general. Every reasonable effort will be made to make these selection lines available to other investigators who might wish to use them.
