The primary aim of this RSDA application is to release Dr. Young from the majority of her undergraduate teaching and administrative responsibilities so that she can devote increased time and effort to drug abuse research and research training. Specifically, she will devote the majority of her time to projects supported by DA03796 (Behavioral pharmacology of opioid tolerance). These projects use drug discrimination assays to assess how pharmacological and behavioral factors modulate the development of tolerance to the discriminative effects of mu opioids, with particular attention to patterns of tolerance and cross-tolerance among opioids that differ in relative intrinsic efficacy. The first project will examine the role of agonist efficacy in patterns of tolerance and cross-tolerance to the morphine-like discriminative stimulus effects of mu opioids. Experiments will examine tolerance to mu agonists during treatment with several doses of morphine, tolerance to the same compounds during treatment with the low efficacy mu agonist nalbuphine, and tolerance during treatment with the high efficacy agonist fentanyl. Tests will examine tolerance produced by a compound to itself, cross-tolerance to other compounds, and any changes in relative potency among compounds as function of repeated treatment. A second project will examine the stimulus effects of opioids in opioid- dependent subjects. A third project will conduct studies with irreversible opioid receptor antagonists, in order to provide an independent test of the hypothesis that differences in tolerance are related to differences in agonist intrinsic efficacy. A fourth project will study the stimulus effects of low efficacy agonists per se, by establishing representative compounds as discriminative stimuli and examining patterns of generalization and cross-tolerance. A final project will examine whether up-regulation of opioid binding sites is followed by differential changes in the stimulus effects of lower and higher efficacy agonists. Dr. Young will also devote time to projects evaluating the pharmacological and behavioral influences of prototypic competitive and non-competitive NMDA antagonists on the development of tolerance to the antinociceptive and discriminative stimulus effects of morphine (MH47181), and to research training supported by MARC (GM08030 and MH17153) and MBRS (RR08167) training grants. These latter grants provide intensive research training for undergraduate and graduate minority students, who participate in the projects described above.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000132-09
Application #
2414536
Study Section
Special Emphasis Panel (SRCD)
Project Start
1988-09-30
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
9
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wayne State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Walker, Ellen A; Young, Alice M (2002) Clocinnamox distinguishes opioid agonists according to relative efficacy in normal and morphine-treated rats trained to discriminate morphine. J Pharmacol Exp Ther 302:101-10
Walker, E A; Young, A M (2001) Differential tolerance to antinociceptive effects of mu opioids during repeated treatment with etonitazene, morphine, or buprenorphine in rats. Psychopharmacology (Berl) 154:131-42
Walker, E A; Zernig, G; Young, A M (1998) In vivo apparent affinity and efficacy estimates for mu opiates in a rat tail-withdrawal assay. Psychopharmacology (Berl) 136:15-23
Makhay, M M; Young, A M; Poling, A (1998) Establishing morphine and U-50,488H as discriminative stimuli in a three-choice assay with pigeons. Exp Clin Psychopharmacol 6:3-9
Walker, E A; Richardson, T M; Young, A M (1997) Tolerance and cross-tolerance to morphine-like stimulus effects of mu opioids in rats. Psychopharmacology (Berl) 133:17-28
Young, A M; McMullen, W J; Makhay, M M et al. (1996) Behavioral contingencies modulate tolerance to discriminative stimulus effects of morphine. Psychopharmacology (Berl) 125:220-30
Walker, E A; Richardson, T M; Young, A M (1996) In vivo apparent pA2 analysis in rats treated with either clocinnamox or morphine. Psychopharmacology (Berl) 125:113-9
Walker, E A; Makhay, M M; House, J D et al. (1994) In vivo apparent pA2 analysis for naltrexone antagonism of discriminative stimulus and analgesic effects of opiate agonists in rats. J Pharmacol Exp Ther 271:959-68
Walker, E A; Young, A M (1993) Discriminative-stimulus effects of the low efficacy mu agonist nalbuphine. J Pharmacol Exp Ther 267:322-30
Young, A M; Masaki, M A; Geula, C (1992) Discriminative stimulus effects of morphine: effects of training dose on agonist and antagonist effects of mu opioids. J Pharmacol Exp Ther 261:246-57

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