Opioids II pp 633-650 | Cite as

Motivational Effects of Opioids

  • T. S. Shippenberg
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 2)

Abstract

A prominent behavioral effect of opiates and other drugs of abuse is their ability to affect both mood and motivational processes. μ-Receptor agonists such as morphine or heroin produce euphoria in humans and function as positive reinforcers in a variety of species, i.e., they maintain those behaviors which lead to their administration. These agents are also characterized by their ability to function as conditioned reinforcers eliciting approach and subsequent preferences for stimuli previously associated with their administration. Furthermore, in some individuals, the reinforcing effects of these drugs may become so marked that they become the primary stimuli which motivate behavior, and the process of compulsive drug-seeking or addiction ensues.

Keywords

Nucleus Accumbens Opioid Receptor Ventral Tegmental Area Conditioned Place Preference Motivational Effect 
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References

  1. Amalric M, Cline EJ, Martinez JL, Bloom FE, Koob GF (1987) Rewarding properties of β-endorphin as measured by conditioned place preference. Psychopharmacology 91:14PubMedCrossRefGoogle Scholar
  2. Bals-Kubik R, Herz A, Shippenberg TS (1988) β-Endorophin-(1–27) is a naturally occurring antagonist of the reinforcing effects of opioids. Naunyn Schmiedebergs Arch Pharmacol 338:392–396PubMedCrossRefGoogle Scholar
  3. Bals-Kubik R, Herz A, Shippenberg TS (1989) Evidence that the aversive effects of opioid antagonists and κ-agonists are centrally mediated. Psychopharmacology 98:203–206PubMedCrossRefGoogle Scholar
  4. Bals-Kubik R, Shippenberg TS, Herz A (1990a) Involvement of μ- and γ-receptors in mediating the reinforcing effects of β-endorphin in the rat. Eur J Pharmacol 175:63–69PubMedCrossRefGoogle Scholar
  5. Bals-Kubik R, Shippenberg TS, Herz A (1990b) Neuroanatomical substrates mediating the motivational effects of opioids. In: van Ree JM, Mulder AH, Wiegant VM, Greidanus TVW (eds) New leads in opioid research. Excerpta Medica, Amsterdam, pp 11–13Google Scholar
  6. Bechara A, van der Kooy D (1987) Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol Biochem Behav 28:227–233PubMedCrossRefGoogle Scholar
  7. Belluzzi JD, Stein L (1977) Enkephalin may mediate euphoria and drive-reduction reward. Nature 266:556–558PubMedCrossRefGoogle Scholar
  8. Bozarth M (1987) Intracranial self-administration procedures for the assessment of drug reinforcement. In: Bozarth M (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 173–188CrossRefGoogle Scholar
  9. Bozarth MA, Wise RA (1981a) Intracranial self-administration of morphine into the ventral tegmental area in rats. Life Sci 28:551–555PubMedCrossRefGoogle Scholar
  10. Bozarth MA, Wise R (1981b) Heroin reward is dependent on a dopaminergic substrate. Life Sci 29: 1881–1886PubMedCrossRefGoogle Scholar
  11. Broekkamp CL, Phillips AG, Cools AR (1979) Facilitation of self-stimulation behavior following intracerebral microinjection of opioids into the ventral tegmental area. Pharmacol Biochem Behav 11:289–295PubMedCrossRefGoogle Scholar
  12. Brown EE, Finlay JM, Wong JTF, Damsma G, Fibiger HC (1991) Behavioral and neurochemical interactions between cocaine and buprenorphine: implications for the pharmacotherapy of cocaine abuse. J Pharmacol Exp Ther 256: 119–126PubMedGoogle Scholar
  13. Carboni E, Imperato A, Perezzanil, DiChiara G (1989a) Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of free moving rats. Neuroscience 28:653–661PubMedCrossRefGoogle Scholar
  14. Carboni E, Acquas E, Frau R, DiChiara G (1989b) Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 164:515–519PubMedCrossRefGoogle Scholar
  15. Carboni E, Acquas E, Leone P, DiChiara G (1989c) 5-HT3 receptor antagonists block morphine- and nicotine- but not amphetamine-induced reward. Psychopharmacology 97:175–178PubMedCrossRefGoogle Scholar
  16. Carr GD, Fibinger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Liebman JM, Cooper SJ (eds) The neuropharmacological basis of reward. Clarendon, Oxford, p 264Google Scholar
  17. Chavkin C, James IF, Goldstein A (1982) Dynorphin is a specific endogenous ligand of the κ-opioid receptor. Science 215:413–415PubMedCrossRefGoogle Scholar
  18. Cotton R, Giles MG, Miller L, Shaw JS, Timms D (1984) ICI 174,864: a highly selective antagonist for the opioid γ-receptor. Eur J Pharmacol 97:331–332PubMedCrossRefGoogle Scholar
  19. DiChiara G, Imperato A (1988a) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the meso limbic system of freely-moving rats. Proc Natl Acad Sci USA 85:5274–5278CrossRefGoogle Scholar
  20. DiChiara G, Imperato A (1988b) Opposite effects of μ- and κ-opioid agonists on dopamine release in the nucleus accumbens and dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244:1067–1080Google Scholar
  21. Dixon DM, Traynor JR (1990) Formation of [Leu5]enkephalin from dynorphin A (1–8) by rat central nervous tissue in vitro. J Neurochem 54:1379–1385PubMedCrossRefGoogle Scholar
  22. Downs DA, Woods JH (1976) Naloxone as a negative reinforcer in rhesus monkeys: effects of dose, schedule, and narcotic regimen. Pharmacol Rev 27:397–436Google Scholar
  23. Dworkin SI, Guerin GF, Conchita CO, Goeders NE, Smith JE (1988) Lack of an effect of 6-hydroxydopamine lesions of the nucleus accumbens on intravenous morphine self-administration. Pharmacol Biochem Behav 30:1051–1057PubMedCrossRefGoogle Scholar
  24. Dymshitz J, Lieblich I (1987) Opiate reinforcement and naloxone aversion, as revealed by place preference paradigm, in two strains of rats. Psychopharmacology 92:473–477PubMedCrossRefGoogle Scholar
  25. Esposito RU, Porrino U, Seeger TF (1989) Brain stimulation reward measurement and mapping by psychophysical techniques and quantitative 2-(14C)deoxyglucose autoradiography. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 421–447Google Scholar
  26. Gaiardi M, Bartoletti M, Bacci A, Gubellini C, Costa M (1991) Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats. Psychopharmacology 103:183–187PubMedCrossRefGoogle Scholar
  27. Glimcher PW, Giovino AA, Margolin DH, Hoebel BG (1984) Endogenous opiate reward induced by an enkephalin inhibitor, thiorphan injected into the ventral midbrain behavioral. Neuroscience 98:262–268Google Scholar
  28. Goeders NE, Lane JD, Smith JE (1984) Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol Biochem Behav 20:451–455PubMedCrossRefGoogle Scholar
  29. Grabowski J, Cherek DR (1983) Conditioning factors in opiate dependence. In: Smith JD, Lane S (eds) The neurobiology of opiate reward processes. Elsevier, Amsterdam, pp 175–210Google Scholar
  30. Grevert P, Goldstein A (1977) Effects of naloxone on experimentally induced ischemic pain and on mood in human subjects. Proc Natl Acad Sci USA 74:1291–1294PubMedCrossRefGoogle Scholar
  31. Grevert P, Goldstein A (1978) Endorphins: naloxone fails to alter experimental pain or mood in humans. Science 199:1093–1095PubMedCrossRefGoogle Scholar
  32. Gysling K, Wang RY (1983) Morphine-induced activation of A10 dopamine neurons in the rat. Brain Res 277:119–127PubMedCrossRefGoogle Scholar
  33. Herz A, Shippenberg TS (1989) Motivational effects of opioids: neurochemical and neuroanatomical substrates. In: Goldstein A (ed) Molecular and cellular aspects of the drug addictions. Springer, Berlin Heidelberg New York, pp 111–141CrossRefGoogle Scholar
  34. Hoffman DC, Benninger RJ (1986) Feeding behaviour in rats is differentially affected by pimozide treatment depending on prior experience. Pharmacol Biochem Behav 24:259–262PubMedCrossRefGoogle Scholar
  35. Hoffmeister F (1979) Preclinical evaluation of reinforcing and aversive properties of analgesics. In: Beers RF, Bassett EG (eds) Mechanisms of pain and analgesic compounds. Raven, New York, pp 447–466Google Scholar
  36. Hollister LE, Johnson K, Boukhabza D, Gillepsie HK (1981) Aversive effects of naltrexone in subjects not dependent on opiates. Drug Alcohol Depend 8:37–41 Hubner CB, Koob GF (1987) Ventral pallidal lesions produce decreases in cocaine and heroin self-administration in the rat. Proc Soc Neurosci 13:1717Google Scholar
  37. Iwamoto ET (1988) Dynorphin A [1–17] induces “reward” in rats in the place conditioning paradigm. Life Sci 43:503–508PubMedCrossRefGoogle Scholar
  38. Jeziorski M, White FJ (1989) Electrophysiological effects of selective opioid receptor agonists on AlO dopamine (DA) neurons. Soc Neurosci Abstr 15:1001Google Scholar
  39. Katz JC, Goldberg SR (1987) Second-order schedules of drug injection. In: Bozarth MA (ed) Methods of assessing the reinforcing properties of abused drugs. Springer, Berlin Heidelberg New York, pp 105–117CrossRefGoogle Scholar
  40. Katz RJ, Gormezano G (1979) A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs. Pharmacol Biochem Behav 11:231–233PubMedCrossRefGoogle Scholar
  41. Koob GF, Goeders NE (1989) Neuroanatomical substrates of drug selfadministration. In: Cooper SJ, Lieberman JM (eds) The neuropharmacological basis of reward. Clarendon, Oxford, pp 214–263Google Scholar
  42. Koob GF, Pettit HO, Ettenberg A, Bloom FE (1984) Effects of opiate antagonists and their quaternary derivatives on heroin self-administration in the rat. J Pharmacol Exp Ther 229:481–485PubMedGoogle Scholar
  43. Koob GF, Le HT, Creese I (1987) The DH1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci Lett 79:315–320PubMedCrossRefGoogle Scholar
  44. Kornetsky C, Esposito RU (1979) Euphorigenic drugs: effects on the reward pathways of the brain. Fed Proc 38:2473–2476PubMedGoogle Scholar
  45. Lahti RA, Mickelson MM, McCall JM, von Voightlander PF (1985) [3H]-U69593: a highly selective ligand for the κ-opioid receptor. Eur J Pharmacol 109:281–284PubMedCrossRefGoogle Scholar
  46. Lieblich I, Cohen E, Beiles A (1978) Selection for high and low rates of selfstimulation in rats. Physiol Behav 32:1041–1043Google Scholar
  47. Magnan J, Paterson SJ, Tavani A, Kosterlitz HW (1982) The binding spectrum of narcotic analgesic drugs with different agonist and antagonist properties. Naunyn Schmiedebergs Arch Pharmacol 319:197–205PubMedCrossRefGoogle Scholar
  48. Mosberg HI, Hurst R, Hruby VJ, Gee K, Akiyama K, Yamamura HI, Galligan JJ, Burks TF (1983) Bis-penicillamine enkephalins possess highly unproved specificity toward delta opioid receptors. Proc Natl Acad Sci USA 80:5871PubMedCrossRefGoogle Scholar
  49. Mucha RF, Herz A (1985) Motivational properties of κ- and μ-opioid receptor agonists studied with place and taste preference conditioning procedure. Psychopharmacology 86:274–280PubMedCrossRefGoogle Scholar
  50. Mucha RF, Iversen SD (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences: a procedural examination. Psychopharmacology 82:241–247PubMedCrossRefGoogle Scholar
  51. Mucha RF, Millan MJ, Herz A (1985) Aversive properties of naloxone in nondependent (naive) rats may involve blockade of central β-endorphin. Psychopharmacology 86:281–285PubMedCrossRefGoogle Scholar
  52. Nakajima S, McKenzie GM (1986) Reduction of the rewarding effect of brain stimulation by blockade of dopamine D1 receptor with SCH 23390. Pharmacol Biochem Behav 24:919–923PubMedCrossRefGoogle Scholar
  53. Nakajima S, Wise RA (1987) Heroin self-administration in the rat suppressed by SCH 23390. Soc Neurosci Abstr 13:1545Google Scholar
  54. Nomikos GG, Spyraki C, Galanopoulou P, Papadopoulou Z (1986) Amphetamine and morphine induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens. Psychopharmacology 89:26Google Scholar
  55. Olds ME (1982) Reinforcing effects of morphine in the nucleus accumbens. Brain Res 237:429–440PubMedCrossRefGoogle Scholar
  56. Olds J, Milner P (1954) Positive reinforcement produced by electrical stimulation of septal area and other regions. J Comp Physiol Psychol 47:419–427PubMedCrossRefGoogle Scholar
  57. Olds J, Travis RP (1960) Effects of chlorpromazine, meprobamate, pentobarbital and morphine on self-stimulation. J Pharmacol Exp Ther 128:397–404PubMedGoogle Scholar
  58. Pettit HO, Ettenberg A, Bloom FE, Koob GF (1984) Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin selfadministration in rats. Psychopharmacology 84:167–173PubMedCrossRefGoogle Scholar
  59. Pfeiffer A, Brantl V, Herz A, Emrich HG (1986) Psychotomimesis mediated by κ opiate receptors. Science 233:774–776PubMedCrossRefGoogle Scholar
  60. Phillips AG, Le Paine FG (1980) Reinforcing effects of morphine microinjection into the ventral tegmental area. Pharmacol Biochem Behav 12:965–968PubMedCrossRefGoogle Scholar
  61. Roques B, Fournie-Kaluski M, Soroca E, Lecomte J, Malfroy B, Llorens C, Schwartz JC (1980) Thiorphan shows antinociceptive activity in mice. Nature 288:286–288PubMedCrossRefGoogle Scholar
  62. Schoffelmeer ANM, Yao YH, Gioannini TL, Hiller JM, Ofri D, Roques BP, Simon EJ (1990) Cross-linking of human 125I β-endorphin to opioid receptors in rat striatal membranes: biochemical evidence for the existence of a μ/δ) opioid receptor complex. J Pharmacol Exp Ther 253:419–426PubMedGoogle Scholar
  63. Shearman G, Hynes M, Fielding S, Lal H (1977) Clonidine self-administration in the rat: a comparison with fentanyl self-administration. Pharmacologist 19: 171–178Google Scholar
  64. Shippenberg TS, Herz A (1988) Motivational effects of opioids: influence of D-l versus D-2 receptor antagonists. J Pharmacol 151:233–242Google Scholar
  65. Shippenberg TS, Bals-Kubik R, Herz A (1987) Motivational properties of opioids: evidence that an activation of δ-receptors mediates reinforcement processes. Brain Res 436:234–239PubMedCrossRefGoogle Scholar
  66. Shippenberg TS, Emmett-Oglesby MW, Herz A (1988a) Tolerance and selective cross-tolerance to the motivational effects of opioids. Psychopharmacology 96:110–115PubMedCrossRefGoogle Scholar
  67. Shippenberg TS, Stein C, Huber A, Herz A (1988b) Motivational effects of opioids in an animal model of prolonged inflammatory pain: alteration in the effects of κ- but not μ-opioid agonists. Pain 35:179–186PubMedCrossRefGoogle Scholar
  68. Shippenberg TS, Bals-Kubik R, Herz A (1991a) Neuroanatomical substrates mediating the aversive effects of D-l dopamine receptor antagonists. Psychopharmacology 103:209–214PubMedCrossRefGoogle Scholar
  69. Shippenberg TS, Herz A, Spanagel R, Bals-Kubik R (1991b) Neural substrates mediating the motivational effects of opioids. Bioi Psydiatry 2:33–35Google Scholar
  70. Shook JE, Kazmierski W, Wire W, Lemcke PK, Hruby VJ, Burks TF (1988) Opioid receptor selectivity of β-endorphin in vitro and in vivo: μ, δ and ε receptors. J Pharmacol Exp Ther 246: 1018PubMedGoogle Scholar
  71. Smith JE, Lane JD (1983) Brain neurotransmitter turnover correlated with morphine self-administration. In: Smith JE, Lane JD (eds) The neurobiology of opiate reward processes. Elsevier, Amsterdam, pp 361–402Google Scholar
  72. Smith JE, Guerin GF, Co C, Barr TS, Lane JD (1985) Effects of 6–OHDA lesions of the central medical nucleus accumbens on rat intravenous morphine selfadministration. Pharmacol Biochem Behav 23:843–849PubMedCrossRefGoogle Scholar
  73. Smith JE, Shulz K, Co C, Goeders NE, Dworkin ST (1987) Effects of 5,7- dihydroxytryptamine lesions of the cucleus accumbens on rat intravenous morphine self-administration. Pharmacol Biochem Behav 26:607–612PubMedCrossRefGoogle Scholar
  74. Spanagel R, Herz A, Shippenberg TS (1990a) The influence of opioid peptides on dopamine release in the nucleus accumbens: an in-vivo microdialysis study. J Neurochem 55:1734–1740PubMedCrossRefGoogle Scholar
  75. Spanagel R, Herz A, Shippenberg TS (1990b) Identification of the opioid receptor types mediating β-endorphin-induced alterations in dopamine release in the nucleus accumbens. Eur J Pharmacol 190:177–184PubMedCrossRefGoogle Scholar
  76. Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci (No 4) (in press)Google Scholar
  77. Spealman RD, Goldberg SR (1978) Drug self-administration by laboratory animals: control by schedules of reinforcement. Annu Rev Pharmacol Toxicol 18:313–339PubMedCrossRefGoogle Scholar
  78. Spyraki C, Fibiger HC (1988) A role of the mesolimbic dopamine system in the reinforcing properties of diazepam. Psychopharmacology 18:133–137CrossRefGoogle Scholar
  79. Spyraki C, Fibiger HC, Phillips AG (1982) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193PubMedCrossRefGoogle Scholar
  80. Spyraki C, Fibiger HC, Phillips AG (1983) Attenuation of heroin reward in rats by disruption of the meso limbic dopamine system. Psychopharmacology 79:278–283PubMedCrossRefGoogle Scholar
  81. Stapleton JM, Lind MD, Merriman VJ, Bozarth MA, Reid LD (1979) Affective consequences and subsequent effects on morphine self-administration of D-Ala2-methionine enkephalin. Physiol Psychol 7:146–152Google Scholar
  82. Steinfels GF, Young AG, Khazan N (1982) Self-administration of nalbuphine, butorphanol and pentazocine by morphine post-addict rats. Pharmacol Biochem Behav 16:167–171PubMedCrossRefGoogle Scholar
  83. Stevens KE, Shiotsu G, Stein C (1991) Hippocampal μ-receptors mediate opioid reinforcement in the CA3 region. Brain Res 545:8–16PubMedCrossRefGoogle Scholar
  84. Stolerman IP (1985) Motivational effects of opioids evidence on the role of endorphins in mediating reward or aversion. Pharmacol Biochem Behav 23:877–881PubMedCrossRefGoogle Scholar
  85. Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9:321–353PubMedCrossRefGoogle Scholar
  86. Tachibana S, Oshino H, Arakawa Y, Nakzawa T, Araki S, Kaneko T, Yamatsu K, Miyagawa H (1988) Design and synthesis of metabolically stable analogs of dynorphin-A and their analgesic characteristics. In: Naito Foundation, 22–24 October 1987. University of Tokyo Press, TokyoGoogle Scholar
  87. Vaccarino FJ, Floyd EB, Koob GF (1985a) Blockade of nucleus accumbens opiate receptors attenuates intravenous heroin reward in the rat. Psychopharmacology 86:37–42PubMedCrossRefGoogle Scholar
  88. Vaccarino FJ, Pettit HO, Bloom FE, Koob GF (1985b) Effects of intracerebroventricular administration of methyl-naloxonium chloride on heroin selfadministration in the rat. Pharmacol Biochem Behav 23:495–498PubMedCrossRefGoogle Scholar
  89. Van der Kooy D, Mucha RF, O’Shaughnessy M, Buceneiks P (1982) Reinforcing effects of brain microinjections of morphine revealed by conditioned place preference. Brain Res 243:107–117PubMedCrossRefGoogle Scholar
  90. Van Ree JM, Smyth DG, Colpaert FC (1979) Dependence creating properties of lipotropin C-fragment (β-endorphin): evidence for its internal control of behaviour. Life Sci 24:495–502PubMedCrossRefGoogle Scholar
  91. Von Voightlander PF, Lahti RA, Ludens IH (1983) U50,488H: a selective and structurally novel non-mu (kappa) opioid agonist. J Pharmacol Exp Ther 224:7–11Google Scholar
  92. White NM, Packard MG, Hiroi N (1991) Place conditioning with dopamine D1 and D2 agonists injected peripherally or into the nucleus accumbens. Psychopharmacology 103:271–276PubMedCrossRefGoogle Scholar
  93. Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225PubMedCrossRefGoogle Scholar
  94. Wolf P, Olpe HR, Avrith D, Haas HL (1978) GABAergic inhibition of neurons in the ventral tegmental area. Experientia 34:73–74PubMedCrossRefGoogle Scholar
  95. Woods IH, Young AM, Herling S (1982) Classification of narcotics on the basis of their reinforcing, discriminative and antagonist effects in rhesus monkeys. Fed Proc 41:221–227PubMedGoogle Scholar
  96. Zito KA, Vickers G, Roberts DCS (1985) Disruption of cocaine and heroin selfadministration following kainic acid lesions of the nucleus accumbens. Pharmacol Biochem Behav 23: 1029–1036PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1993

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  • T. S. Shippenberg

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