Behavioral Pharmacology of Opiates

  • James P. Zacny
  • Ellen A. Walker
Chapter

Abstract

The purpose of this chapter is to describe and discuss what is currently known about the behavioral pharmacology of opioids in infra-humans and humans. This is a daunting task, given the breadth and depth of research that has been conducted during the past 50 years. Several reviews on the behavioral pharmacology of opioids cover certain areas in much greater detail than what can be covered here; the reader is encouraged to refer to these reviews, some of which appear yearly as an “update” (see Appendix for review bibliography).*

Keywords

Rhesus Monkey Conditioned Place Preference Discriminative Stimulus Stimulus Effect Subjective Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Aigner, B., and Balster, R. L. (1979). Rapid substitution procedure for iv drug self-administration studies in rhesus monkeys. Pharmacology, Biochemistry and Behavior; 10, 105–112.Google Scholar
  2. Almaric, M., Cline, E., Martinez, J., Jr., Bloom, F. E., and Koob, G. (1987). Rewarding properties of beta-endorphin as measured by conditioned place preference. Psychopharmacology, 91, 14–19.Google Scholar
  3. Angle, H. V, Knowles, R. R., Marrazzi, A. S., and Sletten, I. W. (1973). Method for self-administering methadone by the heroin addict. International Journal of the Addictions. 8. 435–441.PubMedGoogle Scholar
  4. Bals-Kubik, R., Herz, A., and Shippenberg, T. (1989). Evidence that the aversive effects of opioid antagonists and k-agonists are centrally mediated. Psvchopharmacologv, 98, 203–206.Google Scholar
  5. Bals-Kubik, R., Shippenberg, T. S., and Herz, A. (1990a). Involvement of central mu and delta opioid receptors in mediating the reinforcing effects of beta-endorphin in the rat. European Journal of Pharmacology, 175, 63–69.PubMedGoogle Scholar
  6. Bals-Kubik, R., Shippenberg, T. S., and Herz, A. (1990b). Neuroanatomical substrates mediating the motivational effects of opioids. In J. van Ree, A. Mulder, V. Wiegart, and T. van Wimersma-Geidarus (Eds.), New Leads in Opioid Research. Proceedings of the International Narcotics Research Conference (pp. 11–12 ). Amsterdam: Exerpta Medica.Google Scholar
  7. Balster, R. L. (1989). Substitution and antagonism in rats trained to discriminate (+)-n-allylnormetazocine from saline. Journal of Pharmacology and Experimental Therapeutics, 249, 749–756.PubMedGoogle Scholar
  8. Balster, R. L., and Lukas, S. E. (1985). Review of self-administration. Drug and Alcohol Dependence, 14, 249–261.PubMedGoogle Scholar
  9. Bechara, S., and van der Kooy, D. (1987). Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacology, Biochemistry and Behavior, 28, 227–233.Google Scholar
  10. Bellville, J. W, and Green, J. (1965). The respiratory and subjective effects of pentazocine. Clinical Pharmacology and Therapeutics, 6, 152–159.PubMedGoogle Scholar
  11. Bergman, J., and Carey, G. (1996). Antagonism of the discriminative stimulus effects of enadoline. In L. S. Harris (Ed.), Problems of drug dependence 1996 (NIDA Research Monograph No. 174, p. 312 ). Washington, DC: U.S. Government Printing Office.Google Scholar
  12. Berman, M. L., Briggs, G. G., Bogh, P., Mannel, R., Manetta, A., and DiSaia, P. J. (1990). Simplified postoperative patient-controlled analgesia on a gynecology-oncology service. Gynecologic Oncology, 38, 55–58.Google Scholar
  13. Bertalmio, A. J., and Woods, J. H. (1987). Differentiation between mu and kappa receptor-mediated effects in opioid drug discrimination: Apparent pA2 analysis. Journal of Pharmacology and Experimental Therapeutics, 243, 591–597.PubMedGoogle Scholar
  14. Bertalmio, A. J., and Woods, J. H. (1989). Reinforcing effect of alfentanil is mediated by mu opioid receptors: Apparent pA, analysis. Journal of Pharmacology and Experimental Therapeutics, 251, 455–460.Google Scholar
  15. Bertalmio, A. J., Herling, S., Hampton, R., Winger, G., and Woods, J. H. (1982). A procedure for rapid evaluation of the discriminative stimulus effects of drugs. Journal of Pharmacological Methods, 7, 289–299.PubMedGoogle Scholar
  16. Bickel, W. K., Higgins, S. T., and Stitzer. M. L. (1986). Choice of blind methadone dose increases by methadone maintenance patients. Drug and Alcohol Dependence, 18, 165–171.PubMedGoogle Scholar
  17. Bigelow, G. E., and Preston, K. L. (1995). Opioids. In F. E. Bloom and D. J. Kupfer (Eds.), Psychopharnracologv: The fourth generation of progress (pp. 1731–1744 ). New York: Raven.Google Scholar
  18. Boccuni, M., Cangi, F., Fusco, B. M., Curradi, C., and Sicuteri, F. (1987). Pentazocine in migraine: Subjective and pupillary abnormal effects. Headache, 27, 503–508.PubMedGoogle Scholar
  19. Butelman, E. R., Winger, G., Zernig, G., and Woods. J. H. (1995). Butorphanol: Characterization of agonist and antagonist effects in rhesus monkey. Journal of Pharmacology and Experimental Therapeutics, 272, 845–853.Google Scholar
  20. Carr, G., Fibiger, H., and Phillips, A. (1989). Conditioned place preference as a measure of drug reward. In J. Liebman and S. Cooper (Eds.). The neuropharmacological basis of reward (pp. 264–319 ). New York: Oxford University Press.Google Scholar
  21. Carroll, M. E., and Meisch, R. A. (1978). Etonitazene as a reinforcer: Oral intake of etonitazene by rhesus monkeys. Psychopharmacologv, 59, 225–229.Google Scholar
  22. Chappell, P. B., Leckman, J. F., Scahill, L. D., Hardin, M. T., Anderson, G., and Cohen, D. J. (1993). Neuroendocrine and behavioral effects of the selective rc agonist spiradoline in Tourette’s syndrome: A pilot study. Psychiatry Research, 47, 267–280.PubMedGoogle Scholar
  23. Collins, R., Weeks, J., Cooper, M., Good, R. and Russell, R. (1984). Prediction of abuse liability of drugs using IV self-administration by rats. Psvchopharmacologv, 82, 6–13.Google Scholar
  24. Colpaert, F. C. (1977). Drug-produced cues and states: Some theoretical and methodological inferences. In H. Lal (Ed.), Discriminative stimulus properties of drugs (pp. 5–21 ). New York: Amsterdam.Google Scholar
  25. Colpaert, F. C., Niemegeers, C., and Janssen. P. A. (1980). Factors regulating drug cue sensitivity: The effect of training dose in fentanyl-saline discrimination. Neuropharmacology, 19, 705–713.Google Scholar
  26. Colpaert, F. C., Meert, T., De Witte, P. and Schmitt. P. (1982). Further evidence validating adjuvant arthritis as an experimental model of chronic pain in the rat. Life Sciences, 31, 67–75.PubMedGoogle Scholar
  27. Comer, S. D., McNutt, R., Chang, K., DeCosta, B. R., Mosberg, H., and Woods, J. H. (1993). Discriminative stimulus effects of BW373U86: A nonpeptide ligand with selectivity for delta opioid receptors. Journal of Pharmacology and Experimental Therapeutics, 267, 866–874.PubMedGoogle Scholar
  28. Devine, D. P, and Wise, R. A. (1994). Self-administration of morphine, DAMGO, and DPDPE into the ventral tegmental area of the rat. Journal of Neuroscience, 14, 1978–1984.PubMedGoogle Scholar
  29. Downs, D. A., and Woods, J. H. (1975). Fixed-ratio escape and avoidance-escape from naloxone in morphine-dependent monkeys: Effects of naloxone dose andn morphine pretreatment. Journal of Experimental Analysis of Behavior; 23. 415–427.Google Scholar
  30. Downs, D. A., and Woods, J. H. (1976). Naloxone as a negative reinforcer in rhesus monkeys: Effects of dose, schedule, and narcotic regimen. Pharmacological Reviews, 27, 397–406.Google Scholar
  31. Dykstra, L. D., Gmerek, D. E., Winger, G., and Woods, J. H. (1987). Kappa opioids in rhesus monkeys: II. Analysis of the antagonistic actions of quadazocine and Bfunaltrexamine. Journal of Pharmacology and Experimental Therapeutics, 242, 421–427.PubMedGoogle Scholar
  32. Emmett-Olgesby, M., Shippenberg, T., and Herz, A. (1988). Tolerance and cross-tolerance to the discriminative stimulus properties of fentanyl and morphine. Journal of Pharmacology and Experimental Therapeutics, 245, 17–23.Google Scholar
  33. France. C. P., and Woods, J. H. (1985). Opiate agonist-antagonist interactions: Application of a three-key drug discrimination procedure. Journal of Pharmacology and Experimental Therapeutics, 234, 81–89.Google Scholar
  34. France, C. P., and Woods, J. H. (1987). (3-Funaltrexamine antagonizes the discriminative stimulus effects of morphine but not naltrexone in pigeons. Psychopharnracologm, 9/, 213–216.Google Scholar
  35. France. C. P., and Woods, J. H. (1990). Discriminative stimulus effects of opioid agonists in morphine-dependent pigeons. Journal of Pharmacology and Experimental Therapeutics, 254, 626–632.PubMedGoogle Scholar
  36. France, C. P., de Costa, B. R., Jacobson, A. E., Rice, K. C., and Woods, J. H. (1990). Apparent affinity of opioid antagonists in morphine-treated rhesus monkeys discriminating between saline and naltrexone. Journal of Pharmacology and Experimental Therapeutics, 252, 600–604.PubMedGoogle Scholar
  37. France, C. P., Medzihradsky, F., and Woods, J. H. (1994). Comparison of kappa opioids in rhesus monkeys: Behavioral effects and receptor binding affinities. Journal of Pharmacology and Experimental Therapeutics. 268, 47–58.PubMedGoogle Scholar
  38. Fraser, H. F., and Rosenberg, D. E. (1964). Studies on the human addiction liability of 2’-hydroxy-5.9-dimethyl-2-(3,3-dimethylallyl)-6,7-benzomorphan (WIN 20,228): A weak narcotic antagonist. Journal of Pharmacology and Experimental Therapeutics, 143, 149–156.Google Scholar
  39. Fraser. H. F., Martin, W. R., Wolbach, A. B., and Isbell, H. (1961). Addiction liability of an isoquinoline analgesic, 1-(p-chlorophenetyl)-2-methyl-6,7-dimethoxy-1,2,3,4tetrahydrois oquinoline. Clinical Pharmacology and Therapeutics, 2, 287–299.PubMedGoogle Scholar
  40. Fraser, H. F., van Horn, G. G., Martin, W. R., Wolbach, A. B., and Isbell, H. (1961). Methods for evaluating abuse liability. (A) “Attitude” of opiate addicts towards opiate-like drugs. (B) A short-term “direct” addiction test. Journal of Pharmacology and Experimental Therapeutics, 133, 371–387.PubMedGoogle Scholar
  41. Gauvin, D., and Young, A. M. (1989). Effects of prior saline-morphine discrimination by pigeons on three-way discrimination including two morphine doses. Psychopharmacology 98, 222–230.PubMedGoogle Scholar
  42. Gerak, L. R., and France, C. P. (1996). Discriminative stimulus effects of nalbuphine in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 276, 523–531.PubMedGoogle Scholar
  43. Glick, S. D., Maisonneve, I. M., Raucci, J., and Archer, S. (1995). Kappa opioid inhibition of morphine and cocaine self-administration in rats. Brain Research, 681, 147–152.PubMedGoogle Scholar
  44. Gorodetzky, C. W., and Martin, W. R. (1966). A comparison of fentanyl, droperidol, and morphine. Clinical Pharmacology and Therapeutics, 6, 731–739.Google Scholar
  45. Graves, D. A., Arrigo, J. M., Foster, T. S., Baumann, T. J., and Batenhorst, R. L. (1985). Relationship between plasma morphine concentrations and pharmacologic effects in postoperative patients using patient-controlled analgesia. Clinical Pharmacy, 4. 41–47.PubMedGoogle Scholar
  46. Greenwald, M. K., June, H. L., Stitzer, M. L., and Marco, A. P. (1996). Comparative pharmacology of short-acting mu opioids in drug abusers. Journal of Pharmacology and Experimental Therapeutics, 277, 1228–1236.PubMedGoogle Scholar
  47. Haertzen, C. A. (1966). Development of scales based on patterns of drug effects, using the Addiction Research Center Inventory (ARCI). Psychological Reports, 18, 163–194.PubMedGoogle Scholar
  48. Haertzen, C. A. (1970). Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Center Inventory ( ARCI ). Psychopharrnacologia, 18, 366–377.Google Scholar
  49. Hamilton, R. C., Dundee, J. W., Clarke, S. J., Loan, W. B., and Morrison, J. D. (1967). Studies of drugs given before anaesthesia: XIII. Pentazocine and other opiate antagonists. British Journal of Anaesthesia, 39, 647–656.PubMedGoogle Scholar
  50. Hein, D. W., Young, A. M., Herling, S., and Woods, J. H. (1981). Pharmacological analysis of the discriminative stimulus characteristics of ethylketazocine in the rhesus monkey. Journal of Pharmacology and Experimental Therapeutics, 218, 7–15.PubMedGoogle Scholar
  51. Herling, S., Coale, E., Jr., Valentino, R. J.. Hein, D. W., and Woods, J. H. (1980). Narcotic discrimination in pigeons. Journal of Pharmacology and Experimental Therapeutics, 214, 139–146.Google Scholar
  52. Hoffman, D. (1989). The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Research Bulletin, 23, 373–387.PubMedGoogle Scholar
  53. Hoffmeister, F. (1979). Progressive-ratio performance in the rhesus monkey maintained by opiate infusions. Psychopharmacology, 62, 181–186.PubMedGoogle Scholar
  54. Holtzman, S. G. (1982). Discriminative stimulus properties of opioids in the rat and squirrel monkey. In F. C. Colpaert and J. Slangen (Eds.), Drug discrimination: Applications in CNS pharmacology (pp. 17–36 ). Amsterdam: Elsevier Biomedical Press.Google Scholar
  55. Holtzman, S. G. (1983). Discriminative stimulus properties of opioid agonists and antagonists. In S. Cooper (Ed.), Theory in psvchopharmacologv (Vol. 2, pp. 1–45 ). London: Academic Press.Google Scholar
  56. Holtzman, S. (1985). Discriminative stimulus effects of morphine withdrawal in the morphine-dependent rat: Suppression by opiate and nonopiate drugs. Journal of Pharmacology and Experimental Therapeutics, 233, 80–86.PubMedGoogle Scholar
  57. Holtzman, S. G., and Locke, K. W. (1988). Neural mechanisms of drug stimuli: Experimental approaches. Transduction mechanisms of drug stimuli. In F. Colpaert and R. Balster (Eds.), Psychopharmacology (pp. 139–153 ). Berlin: Springer-Verlag.Google Scholar
  58. Holtzman, S. G., and Steinfels, G. F. (1994). Antagonism of the discriminative stimulus effects of the kappa-opioid agonist spiradoline. Psychopharmacology, 116, 243–248.PubMedGoogle Scholar
  59. Holtzman, S. G., Cook, L., and Steinfels, G. F. (1991). Discriminative stimulus effects of spiradoline, a kappaopioid agonist. Psychopharmacology, 105. 447–452.PubMedGoogle Scholar
  60. larbe, T. (1978). Discriminative effects of morphine in the pigeon. Pharmacology, Biochemistry and Behavior 9, 411–416.Google Scholar
  61. Jasinski, D. R., and Mansky, P. A. (1972). Evaluation of nalbuphine for abuse potential. Clinical Pharmacology and Therapeutics, 13, 78–90.PubMedGoogle Scholar
  62. Jasinski, D. R. and Preston, K. L. (1985). Assessment of dezocine for morphine-like subjective effects and miosis. Clinical Pharmacology and Therapeutics 38544–548.Google Scholar
  63. Jasinski, D. R., and Preston, K. L. (1986). Evaluation oftilidine for morphine-like subjective effects and euphoria. Drug and Alcohol Dependence, 18, 273–292.PubMedGoogle Scholar
  64. Jasinski, D. R., Martin, W. R., and Sapira, J. D. (1968). Antagonism of the subjective, behavioral, pupillary, and respiratory depressant effects of cyclazocine by naloxone. Clinical Pharnracologv and Therapeutics, 9. 215–222.Google Scholar
  65. Jasinski, D. R., Martin, W. R., and Haeldke, R. D. (1970). Effects of short-and long-term administration of pentazocine in man. Clinical Pharmacology and Therapeutics 11385–403.Google Scholar
  66. Jewett, D. C.. Mosberg, H.. and Woods, J. H. (1996). Discriminative stimulus effects of a centrally administered, delta-opioid peptide (D-Pen2-D-Pen5-enkephalin in pigeons. Psychopharmacology, 127, 225–229.Google Scholar
  67. Jones, B. E., and Prada, J. A. (1975). Drug-seeking behavior during methadone maintenance. Psychopharmacologia (Berlin), 41, 7–10.Google Scholar
  68. Kitchen, 1., and Kennedy, A. (1990). Effects of 8-opioid receptor antagonist naltrindole on opioid induced in vivo release of corticosterone. In J. van Ree, A. Mulder, V. Wiegant, and T. van Wimersma Griedanus (Eds.), New leads in opioid research (pp. 2321–2322 ). Amsterdam: Excerpta Medica.Google Scholar
  69. Koek, W., and Woods, J. H. (1989). Partial generalization in pigeons trained to discriminate morphine from saline: Applications of receptor theory. Drug Development Research, 16, 169–181.Google Scholar
  70. Koob, G. F. (1992). Neural mechanisms of drug reinforcement. Annals of the New York Academy of Sciences, 654, 171–191.PubMedGoogle Scholar
  71. Kumor, K. M., Haertzen, C. A., Johnson, R. E., Kocher, T., and Jasinski, D. R. (1986). Human psychopharmacology of ketocyclazocine as compared with cyclazocine, morphine and placebo. Journal of Pharmacology and Experimental Therapeutics, 238, 960–968.PubMedGoogle Scholar
  72. Kupers, R., and Gybels, J. (1995). The consumption of fentanyl is increased in rats with nociceptive but not with neuropathic pain. Pain, 60. 137–141.PubMedGoogle Scholar
  73. Lamb, R. J., Preston, K. L., Schindler, C. W., Meisch, R. A., Davis, F., Katz. J. L., Henningfield, J. E., and Goldberg, S. R. (1991). The reinforcing and subjective effects of morphine in post-addicts: A dose-response study. Journal of Pharmacology and Experimental Therapeutics, 259, 1 165–1 173.Google Scholar
  74. Lasagna, L., von Felsinger, J. M., and Beecher, J. K. (1955). Drug-induced mood changes in man. Journal of the American Medical Association, 157, 1006–1020.PubMedGoogle Scholar
  75. Locke, K. W., and Holtzman, S. G. (1985). Characterization of the discriminative stimulus effects of centrally-administered morphine in the rat. Psychopharmacology, 87, 1–6.PubMedGoogle Scholar
  76. Locke, K. W., and Holtzman, S. G. (1986). Behavioral effects of opioid peptides selective for mu or delta receptors: I. Morphine-like discriminative stimulus effects. Journal of Pharmacology and Experimental Therapeutics, 238, 900–906.Google Scholar
  77. Lord, J. A. H., Waterfield, A. A., Hughes, J., and Kosterlitz, H. W. (1977). Endogenous opioid peptides: Multiple agonists and receptors. Nature, 267, 495–499.PubMedGoogle Scholar
  78. Lukas, S. E., Griffiths, R. R., and Brady, J. V. (1983). Buprenorphine self-administration by the baboon: Comparison with other opioids. In L. S. Harris (Ed.), Problems of drug dependence 1982 (NIDA Monograph Series No. 43, pp. 178–183 ). Washington, DC: U.S. Government Printing Office.Google Scholar
  79. Lukas, S. E., Brady, J. V., and Griffiths, R. R. (1986). Comparison of opioid self-injection and disruption of schedule-controlled performance in the baboon. Journal of Pharmacology and Experimental Therapeutics, 238, 924–931.PubMedGoogle Scholar
  80. Martin, T. J., Dworkin, S. I., and Smith. J. E. (1995). Alkylation of mu opioid receptors by (3-funaltrexamine in vivo: Comparison of the effects on in situ binding and heroin self-administration in rats. Journal of Pharmacology and Experimental Therapeutics. 272, 1135–1140.PubMedGoogle Scholar
  81. Martin, W R., and Fraser, H. F. (1961). A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts. Journal of Pharmacology and Experimental Therapeutics, 133, 388–399.PubMedGoogle Scholar
  82. Martin, W. R., Sloan, J. W., Sapira, J. D., and Jasinski, D. R. (1971). Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clinical Pharmacology and Therapeutics, 12, 245–258.PubMedGoogle Scholar
  83. Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E.. and Gilbert, P. E. (1976) The effects of mor-phine-and nalorphine-like drugs in the non-dependent and morphine-dependent chronic spinal dog. Journal of Pharmacology and Experimental Therapeutics. 197, 517–532.PubMedGoogle Scholar
  84. Meisch, R. A. (1995). Oral self-administration of etonitazene in rhesus monkeys: Use of a fading procedure to establish etonitazene as a reinforcer. Pharmacology, Biochemistry and Behavior, 50, 571–580.Google Scholar
  85. Mello, N. K., Bree, M., and Mendelson, J. (1981). Buprenorphine self-administration by rhesus monkeys. Pharmacology, Biochemistry and Behavior, 15, 215–225.Google Scholar
  86. Mello, N. K.. Mendelson, J. H., Kuehnle, J. C., and Sellers, M. S. (1981). Operant analysis of human heroin self-administration and the effects of naltrexone. Journal of Pharmacology and Experimental Therapeutics, 216, 45–54.PubMedGoogle Scholar
  87. Mello, N. K., Mendelson, J. H., and Kuehnle, J. C. (1982). Buprenorphine effects on human heroin self-administration: an operant analysis. Journal of Pharmacology and Experimental Therapeutics, 223, 30–39.PubMedGoogle Scholar
  88. Mello, N. K.. Bree, M., and Mendelson, J. (1983). Comparison of buprenorphine and methadone effects on opiate self-administration. Journal of Pharmacology and Experimental Therapeutics, 225, 378–386.Google Scholar
  89. Mello, N. K., Mendelson, J., Bree, M., and Lukas, S. E. (1989). Buprenorphine suppresses cocaine self-administration by rhesus monkeys. Science, 245, 859–862.PubMedGoogle Scholar
  90. Mello, N. K.. Lukas. S. E., Kamien, J. B., Mendelson, J. H., Drieze, J., and Cone, E. J. (1992). The effects of chronic buprenorphine treatment on cocaine and food self-administration by rhesus monkeys. Journal of Pharmacology’ and Experimental Therapeutics, 260, 1185–1193.PubMedGoogle Scholar
  91. Miksic, L., and LaI, H. (1977). Tolerance to morphine-produced discriminative stimuli and analgesia. Psychopharmacology. 54, 217–211.PubMedGoogle Scholar
  92. Mucha, R., and Herz, A. (1985). Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacologv, 86. 274–280.Google Scholar
  93. Negus, S. S., Burke, T. F., Medzihradsky, F., and Woods, J. H. (1993). Effects of opioid agonists selective for mu, kappa, and delta opioid receptors on schedule-controlled responding in rhesus monkeys: Antagonism by quadazocine. Journal of Pharmacology and Experimental Therapeutics. 267, 896–902.PubMedGoogle Scholar
  94. Negus, S. S., Butelman, E. R., Chang, K., DeCosta, B., Winger, G., and Woods, J. H. (1994). Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 270, 1025–1034.PubMedGoogle Scholar
  95. Negus, S. S., Mello, N. K., Portoghese, P. S., Lukas, S. E., and Mendelson, J. H. (1995). Role of delta opioid receptors in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 273, 1245–1256.PubMedGoogle Scholar
  96. Pande, A. C., Pyke, R. E., Greiner, M., Wideman, G. L., Benjamin, R., and Pierce, M. W. (1996). Analgesic efficacy of enadoline versus placebo or morphine in postsurgical pain. Clinical Neuropharnracologv, 19, 451–456.Google Scholar
  97. Parker, R. K., Holtmann, B., and White, P. F. (1991). Patient-controlled analgesia: Does a concurrent opioid infusion improve pain management after surgery? Journal of the American Medical Association, 266, 1947–1952.PubMedGoogle Scholar
  98. Paronis, C. A., and Holtzman, S. G. (1994). Sensitization and tolerance to the discriminative stimulus effects of mu-opioid agonists. Psvchopharnracolog. 114, 601–310.Google Scholar
  99. Pfeiffer, A., Branti, V., Herz, A., and Emrich, H. M. (1986). Psychotomimesis mediated by opiate receptors. Science, 233, 774–776.PubMedGoogle Scholar
  100. Pickens, R., Meisch, R. A., and Thompson, T. (1978). Drug self-administration: An analysis of the reinforcing effects of drugs. In L. L. Iversen, D. Iversen, and S. Snyder (Eds.), Handbook of psvchopharmacology (pp. 1–7 ). New York: Plenum.Google Scholar
  101. Picker, M. J. (1991). Discriminative stimulus properties of (+)- and (-)-n-allylnormetazocine: The role of training dose in the stimulus substitution patterns produced by PCP/sigma and mixed action opioid compounds. Behavioural Pharnracologv, 2, 497–511.Google Scholar
  102. Picker, M. J. (1994). Kappa agonist and antagonist properties of mixed action opioids in a pigeon drug discrimination procedure. Journal of Pharmacology and Experimental Therapeutics, 268, 1 190–1 198.Google Scholar
  103. Picker, M. J. (1995). Assessment of the kappa agonist and antagonist properties of mixed action opioids, mu opioids, and a delta opioid in pigeons. Experimental and Clinical Psychopharmacology, 3, 240.Google Scholar
  104. Picker, M. J., and Dykstra, L. A. (1987). Comparison of the discriminative stimulus properties of U50,488 and morphine in pigeons. Journal of Pharmacology and Experimental Therapeutics, 243, 938–945.PubMedGoogle Scholar
  105. Picker, M. J., and Dykstra, L. A. (1989). Discriminative stimulus effects of mu and kappa opioids in the pigeon: Analysis of the effects of full and partial mu and kappa agonists. Journal of Pharmacology and Experimental Therapeutics, 249, 557–566.PubMedGoogle Scholar
  106. Picker, M. J., Negus, S. S., and Dykstra, L. A. (1989). Opioid-like discriminative stimulus properties of benzomorphans in the pigeon: Stereospecificity and differential substitution patterns. Life Sciences, 45, 1637–1645.PubMedGoogle Scholar
  107. Picker, M. J., Yarbrough, J., Hughes, C. E., Smith, M. A., Morgan, D., and Dykstra, L. A. (1993). Agonist and antagonist effects of mixed action opioids in the pigeon drug discrimination procedure: Influence of training dose, intrinsic efficacy and interanimal differences. Journal of Pharmacology and Experimental Therapeutics, 266, 756–767.PubMedGoogle Scholar
  108. Picker, M. J., Benyas, S., Horwitz, J., Thompson, K., Mathewson, C., and Smith, M. A. (1996). Discrimina-tive stimulus effects of butorphanol: Influence of training dose on the substitution patterns produced by mu, kappa, and delta opioids. Journal of Pharmacology and Experimental Therapeutics, 279, 1130–1141.PubMedGoogle Scholar
  109. Preston, K. L., and Bigelow, G. E. (1993). Differential naltrexone antagonism of hydromorphine and pentazocine effects in human volunteers. Journal of Pharmacology and Experimental Therapeutics, 264, 813–823.PubMedGoogle Scholar
  110. Preston, K. L., and Bigelow, G. E. (1994). Drug discrimination assessment of agonist—antagonist opioids in humans: a three-choice saline-hydromorphonebutorphanol procedure. Journal of Pharmacology and Experimental Therapeutics, 271, 48–60.PubMedGoogle Scholar
  111. Preston, K. L., and Jasinski, D. R. (1991). Abuse liability studies of opioid agonist—antagonists in humans. Drug and Alcohol Dependence, 28, 49–82.PubMedGoogle Scholar
  112. Preston, K. L., Bigelow, G. E., and Liebson, I. A. (1985). Self-administration of clonidine, oxazepam, and hydromorphone by patients undergoing methadone detoxification. Clinical Pharmacology and Therapeutics, 38, 219–227.PubMedGoogle Scholar
  113. Preston, K. L., Bigelow, G. E., Bickel, W., and Liebson, I. A. (1987). Three-choice drug discrimination in opioiddependent humans: Hydromorphone, naloxone and saline. Journal of Pharmacology and Experimental Therapeutics, 243, 1002–1009.Google Scholar
  114. Preston, K. L., Bigelow, G. E., and Liebson, 1. A. (1987). Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts. Journal of Pharmacology and Experimental Therapeutics, 240, 900–910.PubMedGoogle Scholar
  115. Preston, K. L., Bigelow, G. E., and Liebson, I. A. (1988). Butorphanol-precipitated withdrawal in opioiddependent human volunteers. Journal of Pharmacology and Experimental Therapeutics. 246, 441–448.PubMedGoogle Scholar
  116. Preston, K. L., Bigelow, G. E., Bickel, W. K., and Liebson, I. A. (1989). Drug discrimination in human post-addicts: Agonist—antagonist opioids. Journal of Pharmacology and Experimental Therapeutics, 250, 184–196.Google Scholar
  117. Preston, K. L., Bigelow, G. E., and Liebson, I. A. (1989). Antagonist effects of nalbuphine in opioid-dependent human volunteers. Journal of Pharmacology and Experimental Therapeutics, 248, 929–937.PubMedGoogle Scholar
  118. Preston, K. L., Bigelow, G. E., and Liebson, I. A. (1990). Discrimination of butorphanol and nalbuphine in opioid-dependent humans. Pharmacology, Biochemistry and Behavior; 37, 511–522.Google Scholar
  119. Preston, K. L., Liebson, I. A., and Bigelow, G. E. (1992). Discrimination of agonist—antagonist opioids in humans trained on a two-choice saline-hydromorphone discrimination. Journal of Pharmacology and Experimental Therapeutics, 261, 62–71.PubMedGoogle Scholar
  120. Schaefer, G. J., and Holtzman, S. G. (1977). Discriminative effects of morphine in the squirrel monkey. Journal of Pharmacology and Experimental Therapeutics, 201, 67–75.PubMedGoogle Scholar
  121. Schechter, N. L., Berrien, F. B., and Katz, S. M. (1988). The use of patient-controlled analgesia in adolescents with sickle cell crisis pain: A preliminary report. Journal of Pain and Symptom Management, 2, 109–113.Google Scholar
  122. Schuster, C. R. (1976). Drugs as reinforcers in monkey and man. Pharmacological Reviews, 27, 511–521.Google Scholar
  123. Schuster, C. R., Smith, B. B., and Jaffe, J. H. (1971). Drug abuse in heroin users: An experimental study of self-administration of methadone, codeine, and pentazocine. Archives of General Psychiatry, 24, 359–362.PubMedGoogle Scholar
  124. Shannon, H., and Holtzman, S. G. (1979). Morphine training dose: A determinant of stimulus generalization to narcotic antagonists in the rat. Psvchopharnmcologu 61, 239–244.Google Scholar
  125. Shannon, H. E. (1983). Pharmacological evaluation of nallylnormetazocine (SKF 10,047) on the basis of its discriminative stimulus properties in the rat. Journal of Pharmacology and Experimental Therapeutics, 225, 144–152.PubMedGoogle Scholar
  126. Shannon, H. E., and Holtzman, S. G. (1976). Evaluation of the discriminative stimulus effects of morphine in the rat. Journal of Pharmacology and Experimental Therapeutics, 198, 54–65.PubMedGoogle Scholar
  127. Shearman, G., and Herz, A. (1981). Discriminative stimulus properties of bremazocine in the rat. Neuropharmacology, 20, 1209–1213.PubMedGoogle Scholar
  128. Shearman, G., and Herz, A. (1982). Evidence that the discriminative stimulus properties of fentanyl and ethylketocyclazocine are mediated by an interaction with different opiate receptors. Journal of Pharmacology and Experimental Therapeutics, 221, 735–739.PubMedGoogle Scholar
  129. Shippenberg, T. S., and Bals-Kubik, R. (1991). Motivational aspects of opioids: Neurochemical and neuroanatomical substrates. In O. Almedia and T. S. Shippenberg (Eds.), The neurobiology of opioids (pp. 331–350 ). New York: Springer-Verlag.Google Scholar
  130. Shippenberg, T. S., Bals-Kubik, R., and Herz, A. (1987). Motivational properties of opioids: Evidence that an activation of delta-receptors mediates reinforcement processes. Brain Research, 436, 234–239.PubMedGoogle Scholar
  131. Slifer, B., and Balster, R. L. (1983). Reinforcing properties of stereoisomers of the putative sigma agonists Nallynormetazocine and cyclazocine in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 225, 522–528.PubMedGoogle Scholar
  132. Spiga, R., Grabowski, J., Silverman, P. B., and Meisch, R. A. (1996). Human methadone self-administration: Effects of dose and ratio requirement. Behavioural Pharmacology, 7, 130–137.Google Scholar
  133. Stitzer, M., Bigelow, G., and Liebson, I. (1979). Supplementary methadone self administration among methadone maintenance clients. Addictive Behaviors, 4, 61–66.PubMedGoogle Scholar
  134. Stitzer, M. L., McCaul, M. E., Bigelow, G. E., and Liebson, I. A. (1983). Oral methadone self-administration: Effects of dose and alternative reinforcers. Clinical Pharmacology and Therapeutics, 34, 29–35.Google Scholar
  135. Strain, E. C., Preston, K. L., Liebson, I. A., and Bigelow, G. E. (1992). Acute effects of buprenorphine, hydromorphone and naloxone in methadone-maintained volunteers. Journal of Pharmacology and Experimental Therapeutics. 261, 985–993.PubMedGoogle Scholar
  136. Strain, E. C., Preston, K. L., Liebson, I. A., and Bigelow, G. E. (1993). Precipitated withdrawal by pentazocine in methadone-maintained volunteers. Journal of Pharmacology and Experimental Therapeutics, 267, 624–634.PubMedGoogle Scholar
  137. Strain, E. C., Preston, K. L., Liebson, I. A., and Bigelow, G. E. (1995). Buprenorphine effects in methadone-maintained volunteers: Effects at two hours after methadone. Journal of Pharmacology and Experimental Therapeutics, 272, 628–638.PubMedGoogle Scholar
  138. Tang, A., and Collins, R. (1985). Behavioral effects of a novel kappa opioid analgesic, U-50,488, in rats and rhesus monkeys. Psychopharmacologu 85, 309–314.Google Scholar
  139. Tang, A. H., and Code, R. A. (1983). Discriminative stimulus properties of nalorphine in the rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics. 227. 563–569.PubMedGoogle Scholar
  140. Teal, J. J., and Holtzman, S. G. (1980a). Discriminative stimulus effects of cyclazocine in the rat. Journal of Pharmacology and Experimental Therapeutics, 212, 368–376.PubMedGoogle Scholar
  141. Teal, J. J., and Holtzman, S. G. (1980b). Stereoselectivity of the stimulus effects of morphine and cyclazocine in squirrel monkeys. Journal of Pharmacology and Experimental Therapeutics, 215. 369–376.PubMedGoogle Scholar
  142. Thompson, T., and Schuster, C. R. (1964). Morphine self-administration, food-reinforced, and avoidance behaviors in rhesus monkeys. Psychopharmacologia. 5. 87–94Google Scholar
  143. Ukai, M., and Holtzman, S. G. (1988). Morphine-like discriminative stimulus effects of opioid peptides: Possible modulatory role of D-Ala’-D-Leu`-enkephalin (DADL) and dynorphin A(1–13). Psychopharmacologu 94, 32–37.Google Scholar
  144. Vanecek, S., and Young, A. (1995). Pharmacological characterization of an operant discrimination among two doses of morphine and saline in pigeons. Behavioural Pharmacology, 6, 669–681.PubMedGoogle Scholar
  145. Villarreal, J. E. (1973). The effects of morphine agonists and antagonists on morphine-dependent rhesus monkeys. In H. Kosterlitz, H. Collier, and J. Villarreal (Eds.), Agonist and antagonist actions of analgesic drugs (pp. 73–83 ). Baltimore: University Park Press.Google Scholar
  146. Walker, E. A., and Young, A. M. (1993). Discriminative-stimulus effects of the low efficacy mu agonist nalbuphine. Journal of Pharmacology and Experimental Therapeutics, 267, 322–330.PubMedGoogle Scholar
  147. Walker, E. A., Makhay, M. M., House, J. D., and Young, A. M. (1994). In vivo apparent pA, analysis for naltrexone antagonism of discriminative stimulus and analgesic effects of opiate agonists in rats. Journal of Pharmacology and Experimental Therapeutics, 271, 959–968.PubMedGoogle Scholar
  148. Walsh, S. L.. June, H. L., Schuh, K. J., Preston, K. L., Bigelow, G. E., and Stitzer, M. L. (1995). Effects of buprenorphine and methadone in methadone-maintained subjects. Psychopharmacologu 119, 268–276.Google Scholar
  149. Walsh, S. L., Preston, K. L., Bigelow, G. E., and Stitzer, M. L. (1995). Acute administration of buprenorphine in humans: Partial agonist and blockade effects. Journal of Pharmacology and Experimental Therapeutics. 274, 36I - 372.Google Scholar
  150. White, G. H., and Holtzman, S. G. (1982). Properties of pentazocine as a discriminative stimulus in the squirrel monkey. Journal of Pharmacology and Experimental Therapeutics, 223, 396–401.PubMedGoogle Scholar
  151. White, J., and Holtzman, S. G. (1981). Three-choice drug discrimination in the rat: Morphine, cyclazocine and saline. Journal of Pharmacology and Experimental Therapeutics, 217, 254–262.PubMedGoogle Scholar
  152. White, J. M., and Holtzman, S. (1983). Three-choice drug discrimination: Phencyclidine-like stimulus effects of opioids. Psychopharmacologu 80, 1–9.Google Scholar
  153. Winger, G., and Woods, J. H. (1996). Effects of buprenorphine on behavior maintained by heroin and alfentanil in rhesus monkeys. Behavioural Pharmacology, 7, 155–159.PubMedGoogle Scholar
  154. Winger, G.. Skjoldager, P., and Woods. J. H. (1992). Effects of buprenorphine and other opioid agonists and antagonists on alfentanil-and cocaine-reinforced responding in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics. 26/. 311–317.Google Scholar
  155. Winger. G., Woods, J. H.. and Hursh, S. R. (1996). Behavior maintained by alfentanil or nalbuphine in rhesus monkeys: Fixed-ratio and time-out changes to establish demand curves and relative reinforcing effectiveness. Experimental and Clinical Psychopharmacologu 4, 131–140.Google Scholar
  156. Woods, J. H. (1977). Narcotic-reinforced responding: A rapid screening procedure. In Proceedings of the 39th meeting of the Committee on Problems of Drug Dependence (pp. 420–437 ). Cambridge, MA: National Academy of Sciences.Google Scholar
  157. Woods, J. H., and Winger, G. (1987). Behavioral characterization of opioid mixed agonist-antagonists. Drug and Alcohol Dependence, 20, 303–315.PubMedGoogle Scholar
  158. Woods, J. H., Young, A. M., and Herling, S. (1982). Classification of narcotics on the basis of their reinforcing, discriminative, and antagonist effects in rhesus monkeys. Federation Proceedings, 41, 221–227.PubMedGoogle Scholar
  159. Woods, J. H., France, C. P., and Winger, G. D. (1992). Behavioral pharmacology of buprenorphine: Issues relevant to its potential in treating drug abuse (NIDA Research Monograph Series No. 121, pp. 12–27 ). Rockville, MD: National Institute on Drug Abuse.Google Scholar
  160. Yanagita, T., Katoh, S., Wakasa, Y., and Oinuma, N. (1982). Drug dependence liability of pentazocine evaluated in the rhesus monkey. Central Institute Experimental Animal Preclinical Report, I, 51–57.Google Scholar
  161. Young, A. M. (1991). Discriminative stimulus profiles of psychoactive drugs. In N. K. Mello (Ed.), Ad-ounces in substance abuse, behavioral and biological research (Vol. 4, pp. 139–203N ). London: Kingsley.Google Scholar
  162. Young, A. M., and Stephens, K. (1984). Antagonism of the discriminative stimulus effects of ethylketazocine, cyclazocine, and nalorphine in macaques. Psychopharmacology, 84, 356–361.PubMedGoogle Scholar
  163. Young, A. M., Swain, H. H., and Woods, J. H. (1981). Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys. Psychopharmacology, 74, 329–335.PubMedGoogle Scholar
  164. Young, A. M., Stephens, K. R., Hein, D. W, and Woods, J. H. (1984). Reinforcing and discriminative stimulus properties of mixed agonists-antagonist opioids. Journal of Pharmacology and Experimental Therapeutics, 229, 118–126.PubMedGoogle Scholar
  165. Young, A. M., Kapitsopoulos, G., and Makhay, M. (1991). Tolerance to morphine-like stimulus effects of mu opioid agonists. Journal of Pharmacology and Experimental Therapeutics, 257, 795–805.Google Scholar
  166. Young, A. M., Masaki, M. A., and Geula, C. (1992). Discriminative stimulus effects of morphine: Effects of training dose on agonist and antagonist effects of mu opioids. Journal of Pharmacology and Experimental Therapeutics, 261, 246–257.PubMedGoogle Scholar
  167. Zacny, J. P., Lichtor, J. L., and de Wit, H. (1992). Subjective, behavioral, and physiologic responses to intravenous dezocine in healthy volunteers. Anesthesia and Analgesia, 74, 523–530.PubMedGoogle Scholar
  168. Zacny, J. P., Lichtor, J. L., Zaragoza, J. G., and de Wit, H. (1992). Subjective and behavioral responses to intravenous fentanyl in healthy volunteers. Psychopharmacology, 107, 319–326.PubMedGoogle Scholar
  169. Zacny, J. P., Lichtor, J. L., Binstock, W, Coalson, D. W., Cutter, T., Flemming, D. C., and Glosten, B. (1993). Subjective, behavioral and physiological responses to intravenous meperidine in healthy volunteers. Psychopharmacology, 111, 306–314.PubMedGoogle Scholar
  170. Zacny, J. P., Lichtor, J. L., Flemming, D., Coalson, D. W, and Thompson. W. K. (1994). A dose-response analysis of the subjective, psychomotor, and physiological effects of intravenous morphine in healthy volunteers. Journal of Pharmacology and Experimental Therapeutics, 268, 1–9.PubMedGoogle Scholar
  171. Zacny, J. P., Lichtor, J. L., Thapar, P., Coalson, D. W, Flemming, D., and Thompson, W. K. (1994). Comparing the subjective, psychomotor, and physiological effects of intravenous butorphanol and morphine in healthy volunteers. Journal of Pharmacology and Experimental Therapeutics, 270, 579–588.PubMedGoogle Scholar
  172. Zacny, J. P., McKay, M. A., Toledano, A. Y., Marks, S., Young, C. J., Klock, P. A., and Apfelbaum, J. L. (1996). The effects of a cold-water immersion stressor on the reinforcing and subjective effects of an opioid in healthy volunteers. Drug and Alcohol Dependence, 42, 133–142.PubMedGoogle Scholar

Appendix

  1. Bigelow, G. E., and Preston, K. L. (1995). Opioids. In F. E. Bloom, and D. J. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress (pp. 1731–1744 ). New York: Raven.Google Scholar
  2. Childress. A. R., Hole, A. V, Ehrman, R. N., Robbins, S. J., McLellan, A. T., and O’ Brien, C.P. (1993). Cue reactivity and cue reactivity interventions in drug dependence (NIDA Research Monograph Series No. 137, pp. 73–95 ).Google Scholar
  3. Washington, DC: U.S. Government Printing Office. de Zwaan, M., and Mitchell, J. E. (1992). Opiate antagonists and eating behavior in humans: A review. Journal of Clinical Pharmacology, 32, 1060–1072.Google Scholar
  4. Di Chiara, G., and North, R. A. (1992). Neurobiology of opiate abuse. Trends in the Pharmacological Sciences, 13, 185–193.Google Scholar
  5. Dykstra, L. A. (1996). Opioid analgesics. In C. R. Schuster and M. J. Kuhar (Eds.), Pharmacological aspects of drug dependence (pp. 197–232 ). Berlin: Springer.Google Scholar
  6. Morley, J. E., Levine, A. S., Yim, G. K., and Lowy, M. T. (1983) Opioid modulation of appetite. Neuroscience and Biobehavioral Reviews, 7, 281–305.Google Scholar
  7. Olson, G. A., Olson, R. D., and Kastin, A. J. (1995). Endogenous opioids: 1994. Peptides, 16, 1517–1555. [Note: this is one of a series of articles that date back to 1979 that summarize research from a given year or years on a number of opioid effects on behavior.]Google Scholar
  8. Pfaus, J. G., and Gorzalka, B. B. (1987). Opioids and sexual behavior. Neuroscience and Biobehavioral Reviews, 11, 1–34.PubMedGoogle Scholar
  9. Preston, K. L., and Jasinski, D. R. (1991). Abuse liability studies of opioid agonist-antagonists in humans. Drug and Alcohol Dependence, 28, 49–82.PubMedGoogle Scholar
  10. Schaefer, G. J. (1992). Opiate antagonists and rewarding brain stimulation. Neuroscience and Biobehavioral Reviews, 12, 1–17.Google Scholar
  11. Spanagel, R. (1995). Modulation of drug-induced sensitization processes by endogenous opioid systems. Behavioural Brain Research, 70, 37–49.PubMedGoogle Scholar
  12. Stewart, J., de Wit, H., and Eikelboom, R. (1984). Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychological Review, 91, 251–268.PubMedGoogle Scholar
  13. Young, A. M., and Sannerud, C. A. (1989). Tolerance to drug discriminative stimuli. In A. Goudie and M. Emmett-Oglesby (Eds.), Psychoactive drugs (pp. 221–278 ). Clifton, NJ: Humana.Google Scholar
  14. Zacny, J. P. (1995). A review of the effects of opiates on psychomotor and cognitive functioning in humans. Experimental and Clinical Psychopharmacology. 3, 432–466.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • James P. Zacny
    • 1
  • Ellen A. Walker
    • 2
  1. 1.Department of Anesthesia and Critical CareThe University of ChicagoChicagoUSA
  2. 2.Department of PsychologyUniversity of North Carolina at Chapel HillChapel HillUSA

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