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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
5K05DA000033-15
Application #
2115850
Study Section
Special Emphasis Panel (SRCD (08))
Project Start
1977-09-01
Project End
1992-12-31
Budget Start
1991-09-01
Budget End
1992-12-31
Support Year
15
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Craft, R M; Dykstra, L A (1993) Morphine antagonizes U50,488's effects in a squirrel monkey shock titration procedure. Eur J Pharmacol 234:199-207
Craft, R M; Dykstra, L A (1992) Agonist and antagonist activity of kappa opioids in the squirrel monkey: II. Effect of chronic morphine treatment. J Pharmacol Exp Ther 260:334-42
Picker, M J; Craft, R M; Negus, S S et al. (1992) Intermediate efficacy mu opioids: examination of their morphine-like stimulus effects and response rate-decreasing effects in morphine-tolerant rats. J Pharmacol Exp Ther 263:668-81
Craft, R M; Dykstra, L A (1992) Agonist and antagonist activity of kappa opioids in the squirrel monkey: I. Antinociception and urine output. J Pharmacol Exp Ther 260:327-33
Doty, P; Dysktra, L A; Picker, M J (1992) Delta 9-tetrahydrocannabinol interactions with phencyclidine and ethanol: effects on accuracy and rate of responding. Pharmacol Biochem Behav 43:61-70
Negus, S S; Picker, M J; Dykstra, L A (1991) Interactions between the discriminative stimulus effects of mu and kappa opioid agonists in the squirrel monkey. J Pharmacol Exp Ther 256:149-58
Dykstra, L A; Picker, M J; Powell, K R (1990) Opioid agonists/antagonists in morphine-tolerant squirrel monkeys. Pharmacol Biochem Behav 36:639-44
Dykstra, L A (1990) Butorphanol, levallorphan, nalbuphine and nalorphine as antagonists in the squirrel monkey. J Pharmacol Exp Ther 254:245-52
Picker, M J; Doty, P; Negus, S S et al. (1990) Discriminative stimulus properties of U50,488 and morphine: effects of training dose on stimulus substitution patterns produced by mu and kappa opioid agonists. J Pharmacol Exp Ther 254:13-22
Negus, S S; Picker, M J; Dykstra, L A (1990) Interactions between mu and kappa opioid agonists in the rat drug discrimination procedure. Psychopharmacology (Berl) 102:465-73

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