The objective of this Research Scientist Award is to free Dr. Dykstra of the majority of her administrative and teaching responsibilities so that she can devote her time to a research program focused on the opioid analgesics. In particular emphasis will be placed on compounds which may provide effective pain relief, but with reduced dependence potential. These include buprenorphine, selected kappa agonists and several mixed agonist- antagonists. Analgesic effects will be examined in the squirrel monkey shock titration procedure and in rodent thermal discrimination procedure. For comparison, several other behavioral endpoints will be examined, including schedule-controlled, complex conditional discriminations and drug discrimination behavior. In all of these investigations, emphasis will be placed on the relationship between the behavioral effects of opioid agonists and presumed activity at mu and kappa opioid receptor types. In order to draw relationships between these effects, comparisons will be made on the basis of 1) differing behavioral profiles and potency relationships amongst various opioid agonists 2) the potency of opioid antagonists in attenuating effects of these agonists and 3) the occurrence of cross tolerance between them.
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