A major component of opioid abuse research involves identifying the various biological, pharmacological and environmental factors that contribute to differences in opioid sensitivity across subject populations. One set of factors that exerts a strong influence on sensitivity to the effects of opioids is the social and environmental housing conditions of the subject. Indeed, numerous studies have reported differences in sensitivity to the antinociceptive, locomotor, and rewarding effects of opioids across differentially housed subjects. The purpose of the proposed research project is to perform a systematic examination of the factors contributing to these differences. One factor expected to play a large role in mediating differences in opioid sensitivity between differentially housed subjects is the intrinsic efficacy of the opioid (i.e., its ability to initiate a cellular response after binding to its receptor site). Previous studies examining the relationship between social and environmental housing conditions and opioid sensitivity have typically relied exclusively on high efficacy mu opioids during behavioral testing. This is a potentially significant issue considering recent evidence indicating that differences in opioid sensitivity between many subject populations are most apparent when lower efficacy opioids are tested. In the proposed research project, differences in sensitivity to the antinociceptive, locomotor, and rewarding effects of mu opioids between differentially housed subjects will be examined by testing opioids possessing a range of intrinsic efficacy at the mu receptor. The proposed experiments are designed to identify the conditions under which differences in opioid sensitivity between subject populations are most apparent and provide clues as to the underlying receptor mechanisms mediating these differences.
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