The objective of this Research Scientist Development Award (Level II) is to free Dr. Young of the majority of her teaching and administrative responsibilities so she can focus her efforts on a research program investigating behavioral and pharmacological variables that modify the development and expression of tolerance to opioid agonists and agonist-antagonists. The experimental methods of behavioral pharmacology will be used to identify ways in which the tolerance and dependence produced by acute or repeated opioid administration can be manipulated. The behavioral end-points assessed will include 1) ongoing rates and patterns of schedule-controlled behavior and 2) the discriminative stimulus properties of morphine. Specific experiments will assess the development and degree of tolerance to the rate-altering effects of morphine, etorphine, ad buprenorphine during repeated injection or osmotic infusion. Other experiments will evaluate the behavioral sequelae of long-term administration of the antagonist naltrexone. A third group of experiments will evaluate the contributions of the behavioral demands imposed by the reinforcement schedule to the development of tolerance to the rate-altering effects of morphine. A final group of experiments will assess changes in the discriminative stimulus profile of morphine and related compounds during repeated administration of opioid agonists, antagonists, and mixed agonist-antagonists. Pharmacotherapies are gaining increasing importance in the treatment of human drug abuse. Pre-clinical identification of the behavioral consequences of long-term opioid administration, and of the ways such consequences can be modified by both pharmacological and psychological factors, may have implications for our understanding both of tolerance processes in general and of the factors underlying opiate abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02DA000132-05
Application #
3069512
Study Section
Drug Abuse Clinical and Behavioral Research Review Committee (DACB)
Project Start
1988-09-30
Project End
1994-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Wayne State University
Department
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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