This project proposes to examine a variety of delta opioid agonist and antagonists following systemic administration in mice and rhesus monkeys. Analgesic effects will be evaluated by selective delta receptor antagonist, and antagonist effect will be examined to find differences in selectivity and potency. When agonist effects are obtained in mice they will be characterized in the presence of irreversible antagonist to determine agonist affinity and efficacy at the delta receptor. The presence of delta receptor subtypes will be examined in mice following systemic administration as well. In the rhesus monkey, a variety of behavioral assessment will be carried out, depending upon the nature of the compound under assessment and its pattern of activity in the mouse. If agonist activity has been found in the other assay;s in the mouse, the compound will be assessed for its effects on conditioned, food-reinforced responding and for analgesic activity. If thought to be an antagonist, its spectrum of antagonist activity will be characterized. With this information in hand, a number of secondary assessments will be carried out to determine reinforcing effect, cardiovascular and respiratory effects, and possible tolerance development. In each of the assays, in both the mouse and monkey, there are significant pieces of knowledge yet to be uncovered regarding compounds that have been used by special routes of administration (e.g., i.c.v. and/or i.t.) This proposal seeks to determine these and to incorporate this information in order to improve the subsequent evaluation of delta receptor-mediated behavioral effects.
Showing the most recent 10 out of 15 publications
