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Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse

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Drugs of Abuse

Part of the book series: Methods In Molecular Medicine™ ((MIMM,volume 79))

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Abstract

Chronic drug abuse is a complex behavioral and social phenomenon, that stems from a diverse set of underlying neural mechanisms. However, two defining features of drug addiction make it especially difficult to treat. First, addiction is compulsive—individuals often continue or resume drug use despite a conscious, stated wish to quit. Second, it is persistent—relapse to active drug use can occur despite years of abstinence. This chapter discusses evidence that the inappropriate engagement of neural mechanisms involved in normal associative learning is responsible for these key behavioral aspects of drug addiction. Central to understanding these mechanisms are the distinctions between reward and reinforcement, between goal-directed and automatized behavior, and between information-dense patterns of synaptic plasticity and information-poor neuronal adaptations. This chapter is intended to complement a previous review (1) by elaborating on some particular forms of associative learning that may be central to drug addiction, although limitations of space prevent a full consideration of the many roles that learning has been suggested to play in drug addiction (2–5).

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References

  1. Berke, J. D. and Hyman, S. E. (2000) Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25, 515–532.

    Article  PubMed  CAS  Google Scholar 

  2. Wikler, A. (1971) Some implications of conditioning theory for problems of drug abuse. Behav. Sci. 16, 92–97.

    Article  PubMed  CAS  Google Scholar 

  3. Stewart, J. (1992) Neurobiology of conditioning to drugs of abuse. Ann. NY Acad. Sci. 654, 335–346.

    Article  PubMed  CAS  Google Scholar 

  4. O’Brien, C. P., Childress, A. R., McLellan, A. T., and Ehrman, R. (1992) A learning model of addiction. Res. Publ. Assoc. Res. Nerv. Ment. Dis. 70, 157–177.

    Google Scholar 

  5. Everitt, B. J., Parkinson, J. A., Olmstead, M. C., Arroyo, M., Robledo, P., and Robbins, T. W. (1999) Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems. Ann. NY Acad. Sci. 877, 412–438.

    Article  PubMed  CAS  Google Scholar 

  6. O’Brien, C. P., Childress, A. R., Ehrman, R., and Robbins, S. J. (1998) Conditioning factors in drug abuse: can they explain compulsion? J. Psychopharmacol. 12, 15–22.

    Article  Google Scholar 

  7. Robinson, T. E. and Berridge, K. C. (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Brain Res. Rev. 18, 247–291.

    Article  PubMed  CAS  Google Scholar 

  8. Koob, G. F. and Le Moal, M. (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278, 52–58.

    Article  PubMed  CAS  Google Scholar 

  9. Fiorino, D. F. and Phillips, A. G. (1999) Facilitation of sexual behavior and enhanced dopamine efflux in the nucleus accumbens of male rats after d-amphetamine-induced behavioral sensitization. J. Neurosci. 19, 456–463.

    PubMed  CAS  Google Scholar 

  10. Wyvell, C. L. and Berridge, K. C. (2001) Incentive sensitization by previous amphetamine exposure: increased cue-triggered “wanting” for sucrose reward. J. Neurosci. 21, 7831–7840.

    PubMed  CAS  Google Scholar 

  11. Gawin, F. H. (1991) Cocaine addiction: psychology and neurophysiology. Science 251, 1580–1586.

    Article  PubMed  CAS  Google Scholar 

  12. Eichenbaum, H. and Cohen, N. J. (2001) From Conditioning to Conscious Recollection: Memory Systems of the Brain. Oxford University Press, New York.

    Google Scholar 

  13. White, N. M. and McDonald, R. J. (2002) Multiple parallel memory systems in the brain of the rat. Neurobiol. Learn. Mem. 77, 125–184.

    Article  PubMed  Google Scholar 

  14. Packard, M. G. (2001) On the neurobiology of multiple memory systems: Tolman versus Hull, system interactions and the emotion-memory link. Cogn. Proc. 2, 3–24.

    Google Scholar 

  15. Mishkin, M., Malamut, B., and Bachevalier, J. (1984) Memories and habits: two neural systems, in Neurobiology of Learning and Memory (Lynch, G., McGaugh, J. L., and Weinberger, N. M., eds.), Guildford, New York, pp. 65–77.

    Google Scholar 

  16. Knowlton, B. J., Mangels, J. A., and Squire, L. R. (1996) A neostriatal habit learning system in humans. Science 273, 1399–1402.

    Article  PubMed  CAS  Google Scholar 

  17. Poldrack, R. A., Clark, J., Pare-Blagoev, E. J., et al. (2001) Interactive memory systems in the human brain. Nature 414, 546–550.

    Article  PubMed  CAS  Google Scholar 

  18. Fernandez-Ruiz, J., Wang, J., Aigner, T. G., and Mishkin, M. (2001) Visual habit formation in monkeys with neurotoxic lesions of the ventrocaudal neostriatum. Proc. Natl. Acad. Sci. USA 98, 4196–4201.

    Article  PubMed  CAS  Google Scholar 

  19. Packard, M. G., Hirsh, R., and White, N. M. (1989) Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems. J. Neurosci. 9, 1465–1472.

    PubMed  CAS  Google Scholar 

  20. McDonald, R. J. and White, N. M. (1993) A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. Behav. Neurosci. 107, 3–22.

    Article  PubMed  CAS  Google Scholar 

  21. Packard, M. G. and White, N. M. (1991) Dissociation of hippocampus and caudate nucleus memory systems by posttraining intracerebral injection of dopamine agonists. Behav. Neurosci. 105, 295–306.

    Article  PubMed  CAS  Google Scholar 

  22. Sherry, D. S. and Schacter, D. L. (1987) The evolution of multiple memory systems. Psychol. Rev. 94, 439–454.

    Article  Google Scholar 

  23. Eichenbaum, H. (2000) A cortical-hippocampal system for declarative memory. Nat. Rev. Neurosci. 1, 41–50.

    Article  PubMed  CAS  Google Scholar 

  24. Suzuki, W. A. and Clayton, N. S. (2000) The hippocampus and memory: a comparative and ethological perspective. Curr. Opin. Neurobiol. 10, 768–773.

    Article  PubMed  CAS  Google Scholar 

  25. Tolman, E. C., Ritchie, B. F., and Kalish, D. (1946) Studies in spatial learning. II. Place learning versus response learning. J. Exp. Psychol. 36, 221–229.

    Article  PubMed  CAS  Google Scholar 

  26. Restle, F. (1957) Discrimination of cues in mazes: a resolution of the “place-vs.-response” question. Psychol. Rev. 64, 217–228.

    Article  PubMed  CAS  Google Scholar 

  27. Packard, M. G. (1999) Glutamate infused posttraining into the hippocampus or caudate-putamen differentially strengthens place and response learning. Proc. Natl. Acad. Sci. USA 96, 12881–12886.

    Article  PubMed  CAS  Google Scholar 

  28. Hirsh, R. (1974) The hippocampus and contextual retrieval of information from memory: a theory. Behav. Biol. 12, 421–444.

    Article  PubMed  CAS  Google Scholar 

  29. Devenport, L. D. and Holloway, F. A. (1980) The rat’s resistance to superstition: role of the hippocampus. J. Comp. Physiol. Psychol. 94, 691–705.

    Article  PubMed  CAS  Google Scholar 

  30. Packard, M. G. and McGaugh, J. L. (1996) Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning. Neurobiol. Learn. Mem. 65, 65–72.

    Article  PubMed  CAS  Google Scholar 

  31. Graybiel, A. M. (1998) The basal ganglia and chunking of action repertoires. Neurobiol. Learn. Mem. 70, 119–136.

    Article  PubMed  CAS  Google Scholar 

  32. Reason, J. (1979) Actions not as planned: the price of automatization, in Aspects of Consciousness, Vol. 1: Psychological Issues (Underwood, G. and Stevens, R., eds.), Academic Press, New York.

    Google Scholar 

  33. Balleine, B. W. and Dickinson, A. (1998) Goal-directed instrumental action: contingency and incentive learning and their cortical substrates. Neuropharmacology 37, 407–419.

    Article  PubMed  CAS  Google Scholar 

  34. Sage, J. R. and Knowlton, B. J. (2000) Effects of US devaluation on win-stay and win-shift radial maze performance in rats. Behav. Neurosci. 114, 295–306.

    Article  PubMed  CAS  Google Scholar 

  35. White, N. M. (1989) Reward or reinforcement: what’s the difference? Neurosci. Biobehav. Rev. 13, 181–186.

    Article  PubMed  CAS  Google Scholar 

  36. White, N. M. and Milner, P. M. (1992) The psychobiology of reinforcers. Annu. Rev. Psychol. 43, 443–471.

    Article  PubMed  CAS  Google Scholar 

  37. Goldman-Rakic, P. S. (1987) Circuitry of primate prefrontal cortex and regulation of behavior by representational memory, in Handbook of Physiology, Vol. 5 (Plum, F., ed.), American Physiological Society, Bethesda, MD, pp. 373–417.

    Google Scholar 

  38. Winocur, G. and Eskes, G. (1998) Prefrontal cortex and caudate nucleus in conditional associative learning: dissociated effects of selective brain lesions in rats. Behav. Neurosci. 112, 89–101.

    Article  PubMed  CAS  Google Scholar 

  39. Passingham, R. E. (1993) The Frontal Lobes and Voluntary Action, Vol. 21. Oxford University Press, New York.

    Google Scholar 

  40. Fuster, J. M. (2001) The prefrontal cortex—an update: time is of the essence. Neuron 30, 319–333.

    Article  PubMed  CAS  Google Scholar 

  41. Stuss, D. T. and Levine, B. (2002) Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu. Rev. Psychol. 53, 401–433.

    Article  PubMed  Google Scholar 

  42. Damasio, A. R., Tranel, D., and Damasio, H. (1990) Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli. Behav. Brain Res. 41, 81–94.

    Article  PubMed  CAS  Google Scholar 

  43. Lhermitte, F., Pillon, B., and Serdaru, M. (1986) Human autonomy and the frontal lobes. Part I: Imitation and utilization behavior: a neuropsychological study of 75 patients. Ann. Neurol. 19, 326–334.

    Article  PubMed  CAS  Google Scholar 

  44. Dias, R., Robbins, T. W., and Roberts, A. C. (1996) Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72.

    Article  PubMed  CAS  Google Scholar 

  45. Ragozzino, M. E., Detrick, S., and Kesner, R. P. (1999) Involvement of the prelimbic-infralimbic areas of the rodent prefrontal cortex in behavioral flexibility for place and response learning. J. Neurosci. 19, 4585–4594.

    PubMed  CAS  Google Scholar 

  46. Hasegawa, I., Hayashi, T., and Miyashita, Y. (1999) Memory retrieval under the control of the prefrontal cortex. Ann. Med. 31, 380–387.

    Article  PubMed  CAS  Google Scholar 

  47. Laroche, S., Davis, S., and Jay, T. M. (2000) Plasticity at hippocampal to prefrontal cortex synapses: dual roles in working memory and consolidation. Hippocampus 10, 438–446.

    Article  PubMed  CAS  Google Scholar 

  48. Winocur, G. and Moscovitch, M. (1999) Anterograde and retrograde amnesia after lesions to frontal cortex in rats. J. Neurosci. 19, 9611–9617.

    PubMed  CAS  Google Scholar 

  49. Floresco, S. B., Seamans, J. K., and Phillips, A. G. (1997) Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay. J. Neurosci. 17, 1880–1890.

    PubMed  CAS  Google Scholar 

  50. Berke, J. D. and Eichenbaum, H. B. (2001) Drug addiction and the hippocampus. Science 294, 1235.

    Article  PubMed  CAS  Google Scholar 

  51. Mink, J. W. (1996) The basal ganglia: focused selection and inhibition of competing motor programs. Prog. Neurobiol. 50, 381–425.

    Article  PubMed  CAS  Google Scholar 

  52. Wise, S. P., Murray, E. A., and Gerfen, C. R. (1996) The frontal cortex-basal ganglia system in primates. Crit. Rev. Neurobiol. 10, 317–356.

    PubMed  CAS  Google Scholar 

  53. Cummings, J. L. (1993) Frontal-subcortical circuits and human behavior. Arch. Neurol. 50, 873–880.

    PubMed  CAS  Google Scholar 

  54. Rolls, E. T. (1999) The brain and emotion. Oxford University Press, Oxford.

    Google Scholar 

  55. Gerfen, C. R. and Wilson, C. J. (1996) The basal ganglia, in Handbook of Chemical Neuroanatomy, Vol. 12: Integrated Systems of the CNS, Part III: (Swanson, L. W., Bjorklund, A., and Hökfelt, T., eds.), Elsevier, Amsterdam.

    Google Scholar 

  56. Haber, S. N., Fudge, J. L., and McFarland, N. R. (2000) Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J. Neurosci. 20, 2369–2382.

    PubMed  CAS  Google Scholar 

  57. Joel, D. and Weiner, I. (2000) The connections of the dopaminergic system with the striatum in rats and primates: an analysis with respect to the functional and compartmental organization of the striatum. Neuroscience 96, 451–474.

    Article  PubMed  CAS  Google Scholar 

  58. Bar-Gad, I. and Bergman, H. (2001) Stepping out of the box: information processing in the neural networks of the basal ganglia. Curr. Opin. Neurobiol. 11, 689–695.

    Article  PubMed  CAS  Google Scholar 

  59. Redgrave, P., Prescott, T. J., and Gurney, K. (1999) The basal ganglia: a vertebrate solution to the selection problem? Neuroscience 89, 1009–1023.

    Article  PubMed  CAS  Google Scholar 

  60. Wickens, J. (1990) Striatal dopamine in motor activation and reward-mediated learning: steps towards a unifying model. J. Neural Transm. Gen. Sect. 80, 9–31.

    Article  PubMed  CAS  Google Scholar 

  61. Fallon, J. H. and Loughlin, S. E. (1995) Substantia nigra, in The Rat Nervous System (Paxinos, G., ed.), Academic Press, New York, pp. 215–238.

    Google Scholar 

  62. Schultz, W. (1998) Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27.

    PubMed  CAS  Google Scholar 

  63. Waelti, P., Dickinson, A., and Schultz, W. (2001) Dopamine responses comply with basic assumptions of formal learning theory. Nature 412, 43–48.

    Article  PubMed  CAS  Google Scholar 

  64. Sutton, R. S. and Barto, A. G. (1998) Reinforcement Learning: An Introduction. The MIT Press, Cambridge, MA.

    Google Scholar 

  65. Pennartz, C. M. (1996) The ascending neuromodulatory systems in learning by reinforcement: comparing computational conjectures with experimental findings. Brain Res. Brain Res. Rev. 21, 219–245.

    Article  Google Scholar 

  66. Schultz, W., Apicella, P., and Ljungberg, T. (1993) Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913.

    PubMed  CAS  Google Scholar 

  67. Gonon, F. (1997) Prolonged and extrasynaptic excitatory action of dopamine mediated by D1 receptors in the rat striatum in vivo. J. Neurosci. 17, 5972–5978.

    PubMed  CAS  Google Scholar 

  68. Garris, P. A., Kilpatrick, M., Bunin, M. A., Michael, D., Walker, Q. D., and Wight-man, R. M. (1999) Dissociation of dopamine release in the nucleus accumbens from intracranial self-stimulation. Nature 398, 67–69.

    Article  PubMed  CAS  Google Scholar 

  69. Holland, P. C. (1993) Cognitive aspects of classical conditioning. Curr. Opin. Neurobiol. 3, 230–236.

    Article  PubMed  CAS  Google Scholar 

  70. Legault, M., Rompre, P. P., and Wise, R. A. (2000) Chemical stimulation of the ventral hippocampus elevates nucleus accumbens dopamine by activating dopaminergic neurons of the ventral tegmental area. J. Neurosci. 20, 1635–1642.

    PubMed  CAS  Google Scholar 

  71. Gallagher, M. (2000) The amygdala and associative learning, in The Amygdala: A Functional Analysis, 2nd edit. (Aggleton, J. P., ed.), Oxford University Press, Oxford, pp. 311–329.

    Google Scholar 

  72. Salamone, J. D. (1996) The behavioral neurochemistry of motivation: methodological and conceptual issues in studies of the dynamic activity of nucleus accumbens dopamine. J. Neurosci. Methods 64, 137–149.

    Article  PubMed  CAS  Google Scholar 

  73. Grace, A. A. (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41, 1–24.

    Article  PubMed  CAS  Google Scholar 

  74. Pidoplichko, V. I., DeBiasi, M., Williams, J. T., and Dani, J. A. (1997) Nicotine activates and desensitizes midbrain dopamine neurons. Nature 390, 401–404.

    Article  PubMed  CAS  Google Scholar 

  75. Zhou, F. M., Liang, Y., and Dani, J. A. (2001) Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum. Nat. Neurosci, 4, 1224–1229.

    Article  PubMed  CAS  Google Scholar 

  76. White, N. M. (1996) Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction 91, 921–949.

    Article  PubMed  CAS  Google Scholar 

  77. Everitt, B. J. Cardinal, R. N. Hall, J., Parkinson, J. A., and Robbins, T. W. (2000) Differential involvement of amygdala subsystems in appetitive conditioning and drug addiction, in The Amygdala: A Functional Analysis, 2nd edit. (Aggleton, J. P., ed.), Oxford University Press, Oxford, pp. 353–390.

    Google Scholar 

  78. Rosenkranz, J. A. and Grace, A. A. (2002) Dopamine-mediated modulation of odour-evoked amygdala potentials during pavlovian conditioning. Nature 417, 282–287.

    Article  PubMed  CAS  Google Scholar 

  79. Viaud, M. D. and White, N. M. (1989) Dissociation of visual and olfactory conditioning in the neostriatum of rats. Behav. Brain Res. 32, 31–42.

    Article  PubMed  CAS  Google Scholar 

  80. White, N. M. (1988) Effect of nigrostriatal dopamine depletion on the post-training, memory-improving action of amphetamine. Life Sci. 43, 7–12.

    Article  PubMed  CAS  Google Scholar 

  81. McGaugh, J. L. (2000) Memory—a century of consolidation. Science 287, 248–251.

    Article  PubMed  CAS  Google Scholar 

  82. Packard, M. G., Cahill, L., and McGaugh, J. L. (1994) Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. Proc. Natl. Acad. Sci. USA 91, 8477–8481.

    Article  PubMed  CAS  Google Scholar 

  83. Di Chiara, G. (1998) A motivational learning hypothesis of the role of mesolimbic dopamine in compulsive drug use. J. Psychopharmacol. 12, 54–67.

    Article  PubMed  Google Scholar 

  84. Tiffany, S. T. and Carter, B. L. (1998) Is craving the source of compulsive drug use? J. Psychopharmacol. 12, 23–30.

    Article  PubMed  CAS  Google Scholar 

  85. Koob, G. F., Rocio, M., Carrera, A., et al. (1998) Substance dependence as a compulsive behavior. J. Psychopharmacol. 12, 39–48.

    Article  PubMed  CAS  Google Scholar 

  86. Bigelow, G. E., Brooner, R. K., and Silverman, K. (1998) Competing motivations: drug reinforcement vs non-drug reinforcement. J. Psychopharmacol. 12, 8–14.

    Article  PubMed  CAS  Google Scholar 

  87. Hyman, S. E. (2001) A 28-year-old man addicted to cocaine. JAMA 286, 2586–2594.

    Article  PubMed  CAS  Google Scholar 

  88. Passingham, R. E. (1998) Attention to action, in The Prefrontal Cortex (Roberts, A. C., Robbins, T. W., and Weiskrantz, L., eds.), Oxford University Press, Oxford, pp. 131–143.

    Google Scholar 

  89. James, W. (1890) The Principles of Psychology. Dover, New York (1950 edition).

    Book  Google Scholar 

  90. Tiffany, S. T. (1990) A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. Psychol. Rev. 97, 147–168.

    Article  PubMed  CAS  Google Scholar 

  91. Gawin, F. H. and Khalsa-Denison, M. E. (1996) Is craving mood-driven or self-propelled? Sensitization and “street” stimulant addiction. NIDA Res. Monogr. 163, 224–250.

    PubMed  CAS  Google Scholar 

  92. Rogers, R. D., Everitt, B. J., Baldacchino, A., et al. (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20, 322–339.

    Article  PubMed  CAS  Google Scholar 

  93. Bechara, A., Dolan, S., Denburg, N., Hindes, A., Anderson, S. W., and Nathan, P. E. (2001) Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers. Neuropsychologia 39, 376–389.

    Article  PubMed  CAS  Google Scholar 

  94. Jentsch, J. D. and Taylor, J. R. (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl.) 146, 373–390.

    Article  CAS  Google Scholar 

  95. Evenden, J. L. (1999) Varieties of impulsivity. Psychopharmacology (Berl.), 146, 348–361.

    Article  CAS  Google Scholar 

  96. Robbins, T. W. (1996) Dissociating executive functions of the prefrontal cortex. Philos. Trans. R. Soc. Lond. B Biol. Sci. 351, 1463–1470; discussion 1470–1471.

    Article  PubMed  CAS  Google Scholar 

  97. Shallice, T. and Burgess, P. (1996) The domain of supervisory processes and temporal organization of behaviour. Philos. Trans. R. Soc. Lond. B Biol. Sci. 351, 1405–1411; discussion 1411–1412.

    Article  PubMed  CAS  Google Scholar 

  98. Bechara, A., Damasio, H., and Damasio, A. R. (2000) Emotion, decision making and the orbitofrontal cortex. Cereb. Cortex 10, 295–307.

    Article  PubMed  CAS  Google Scholar 

  99. Schoenbaum, G., Chiba, A. A., and Gallagher, M. (1998) Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nat. Neurosci. 1, 155–159.

    Article  PubMed  CAS  Google Scholar 

  100. Rolls, E. T. (2000) The orbitofrontal cortex and reward. Cereb. Cortex 10, 284–294.

    Article  PubMed  CAS  Google Scholar 

  101. Rowe, J. B., Toni, I., Josephs, O., Frackowiak, R. S., and Passingham, R. E. (2000) The prefrontal cortex: response selection or maintenance within working memory? Science 288, 1656–1660.

    Article  PubMed  CAS  Google Scholar 

  102. Rahman, S., Sahakian, B. J., Cardinal, R. N., Rogers, R. D., and Robbins, T. W. (2001) Decision making and neuropsychiatry. Trends Cogn. Sci. 5, 271–277.

    Article  PubMed  Google Scholar 

  103. Kincaid, A. E., Zheng, T., and Wilson, C. J. (1998) Connectivity and convergence of single corticostriatal axons. J. Neurosci. 18, 4722–4731.

    PubMed  CAS  Google Scholar 

  104. Charpier, S. and Deniau, J. M. (1997) In vivo activity-dependent plasticity at cortico-striatal connections: evidence for physiological long-term potentiation. Proc. Natl. Acad. Sci. USA 94, 7036–7040.

    Article  PubMed  CAS  Google Scholar 

  105. Charpier, S., Mahon, S., and Deniau, J. M. (1999) In vivo induction of striatal long-term potentiation by low-frequency stimulation of the cerebral cortex. Neuroscience 91, 1209–1222.

    Article  PubMed  CAS  Google Scholar 

  106. Reynolds, J. N., Hyland, B. I., and Wickens, J. R. (2001) A cellular mechanism of reward-related learning. Nature 413, 67–70.

    Article  PubMed  CAS  Google Scholar 

  107. Sanes, J. R. and Lichtman, J. W. (1999) Can molecules explain long-term potentiation? Nat. Neurosci. 2, 597–604.

    Article  PubMed  CAS  Google Scholar 

  108. Bailey, C. H., Bartsch, D., and Kandel, E. R. (1996) Toward a molecular definition of long-term memory storage. Proc. Natl. Acad. Sci. USA 93, 13445–13452.

    Article  PubMed  CAS  Google Scholar 

  109. Engert, F. and Bonhoeffer, T. (1999) Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399, 66–70.

    Article  PubMed  CAS  Google Scholar 

  110. Bozdagi, O., Shan, W., Tanaka, H., Benson, D. L., and Huntley, G. W. (2000) Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation. Neuron 28, 245–259.

    Article  PubMed  CAS  Google Scholar 

  111. Robinson, T. E. and Kolb, B. (1997) Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine. J. Neurosci. 17, 8491–8497.

    PubMed  CAS  Google Scholar 

  112. Robinson, T. E. and Kolb, B. (1999) Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine. Eur. J. Neurosci. 11, 1598–1604.

    Article  PubMed  CAS  Google Scholar 

  113. Robinson, T. E. and Kolb, B. (1999) Morphine alters the structure of neurons in the nucleus accumbens and neocortex of rats. Synapse 33, 160–162.

    Article  PubMed  CAS  Google Scholar 

  114. Brown, R. W. and Kolb, B. (2001) Nicotine sensitization increases dendritic length and spine density in the nucleus accumbens and cingulate cortex. Brain Res. 899, 94–100.

    Article  PubMed  CAS  Google Scholar 

  115. Ingham, C. A., Hood, S. H., and Arbuthnott, G. W. (1989) Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res. 503, 334–348.

    Article  PubMed  CAS  Google Scholar 

  116. Ingham, C. A., Hood, S. H., van Maldegem, B., Weenink, A., and Arbuthnott, G. W. (1993) Morphological changes in the rat neostriatum after unilateral 6-hydroxydopamine injections into the nigrostriatal pathway. Exp. Brain Res. 93, 17–27.

    Article  PubMed  CAS  Google Scholar 

  117. Ingham, C. A., Hood, S. H., Taggart, P., and Arbuthnott, G. W. (1998) Plasticity of synapses in the rat neostriatum after unilateral lesion of the nigrostriatal dopaminergic pathway. J. Neurosci. 18, 4732–4743.

    PubMed  CAS  Google Scholar 

  118. Meredith, G. E., Ypma, P., and Zahm, D. S. (1995) Effects of dopamine depletion on the morphology of medium spiny neurons in the shell and core of the rat nucleus accumbens. J. Neurosci. 15, 3808–3820.

    PubMed  CAS  Google Scholar 

  119. Frey, U. and Morris, R. G. (1998) Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci. 21, 181–188.

    Article  PubMed  CAS  Google Scholar 

  120. Milner, B., Squire, L. R., and Kandel, E. R. (1998) Cognitive neuroscience and the study of memory. Neuron 20, 445–468.

    Article  PubMed  CAS  Google Scholar 

  121. Silva, A. J., Kogan, J. H., Frankland, P. W., and Kida, S. (1998) CREB and memory. Annu. Rev. Neurosci. 21, 127–148.

    Article  PubMed  CAS  Google Scholar 

  122. Sanyal, S., Sandstrom, D. J., Hoeffer, C. A., and Ramaswami, M. (2002) AP-1 functions upstream of CREB to control synaptic plasticity in Drosophila. Nature 416, 870–874.

    Article  PubMed  CAS  Google Scholar 

  123. Graybiel, A. M., Moratalla, R., and Robertson, H. A. (1990) Amphetamine and cocaine induce drug-specific activation of the c-fos gene in striosome-matrix compartments and limbic subdivisions of the striatum. Proc. Natl. Acad. Sci. USA 87, 6912–6916.

    Article  PubMed  CAS  Google Scholar 

  124. Cole, A. J., Bhat, R. V., Patt, C., Worley, P. F., and Baraban, J. M. (1992) D1 dopamine receptor activation of multiple transcription factor genes in rat striatum. J. Neurochem. 58, 1420–1426.

    Article  PubMed  CAS  Google Scholar 

  125. Berke, J. D., Paletzki, R. F., Aronson, G. J., Hyman, S. E., and Gerfen, C. R. (1998) A complex program of striatal gene expression induced by dopaminergic stimulation. J. Neurosci. 18, 5301–5310.

    PubMed  CAS  Google Scholar 

  126. Berke, J. D., Sgambato, V., Zhu, P. P., Lavoie, B., Vincent, M., Krause, M., and Hyman, S. E. (2001) Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin. Neuron 32, 277–287.

    Article  PubMed  CAS  Google Scholar 

  127. Bottai, D., Guzowski, J. F., Schwarz, M. K., et al. (2002) Synaptic activity-induced conversion of intronic to exonic sequence in Homer 1 immediate early gene expression. J. Neurosci. 22, 167–175.

    PubMed  CAS  Google Scholar 

  128. Fosnaugh, J. S., Bhat, R. V., Yamagata, K., Worley, P. F., and Baraban, J. M. (1995) Activation of arc, a putative “effector” immediate early gene, by cocaine in rat brain. J. Neurochem. 64, 2377–2380.

    Article  PubMed  CAS  Google Scholar 

  129. Huang, Y. Y. and Kandel, E. R. (1995) D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus. Proc. Natl. Acad. Sci. USA 92, 2446–2450.

    Article  PubMed  CAS  Google Scholar 

  130. Otmakhova, N. A. and Lisman, J. E. (1998) D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism. J. Neurosci. 18, 1270–1279.

    PubMed  CAS  Google Scholar 

  131. Kulla, A. and Manahan-Vaughan, D. (2000) Depotentiation in the dentate gyrus of freely moving rats is modulated by D1/D5 dopamine receptors. Cereb. Cortex 10, 614–620.

    Article  PubMed  CAS  Google Scholar 

  132. Gurden, H., Takita, M., and Jay, T. M. (2000) Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo. J. Neurosci. 20, RC106.

    PubMed  CAS  Google Scholar 

  133. Ungless, M. A., Whistler, J. L., Malenka, R. C., and Bonci, A. (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411, 583–587.

    Article  PubMed  CAS  Google Scholar 

  134. Mansvelder, H. D. and McGehee, D. S. (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27, 349–357.

    Article  PubMed  CAS  Google Scholar 

  135. Nestler, E. J. (2001) Molecular neurobiology of addiction. Am. J. Addict. 10, 201–217.

    Article  PubMed  CAS  Google Scholar 

  136. Stevens, C. F. (1998) A million dollar question: does LTP=memory? Neuron 20, 1–2.

    Article  PubMed  CAS  Google Scholar 

  137. Martin, S. J., Grimwood, P. D., and Morris, R. G. (2000) Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711.

    Article  PubMed  CAS  Google Scholar 

  138. Pittenger, C., Huang, Y. Y., Paletzki, R. F., et al. (2002) Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory. Neuron 34, 447–462.

    Article  PubMed  CAS  Google Scholar 

  139. Cole, R. L., Konradi, C., Douglass, J., and Hyman, S. E. (1995) Neuronal adaptation to amphetamine and dopamine: molecular mechanisms of prodynorphin gene regulation in rat striatum. Neuron 14, 813–823.

    Article  PubMed  CAS  Google Scholar 

  140. Shippenberg, T. S. and Rea, W. (1997) Sensitization to the behavioral effects of cocaine: modulation by dynorphin and kappa-opioid receptor agonists. Pharmacol. Biochem. Behav. 57, 449–455.

    Article  PubMed  CAS  Google Scholar 

  141. Steiner, H. and Gerfen, C. R. (1998) Role of dynorphin and enkephalin in the regulation of striatal output pathways and behavior. Exp. Brain Res. 123, 60–76.

    Article  PubMed  CAS  Google Scholar 

  142. Hurd, Y. L. and Herkenham, M. (1993) Molecular alterations in the neostriatum of human cocaine addicts. Synapse 13, 357–369.

    Article  PubMed  CAS  Google Scholar 

  143. Carlezon, W. A., Jr., Thome, J., Olson, V. G., et al. (1998) Regulation of cocaine reward by CREB. Science 282, 2272–2275.

    Article  PubMed  CAS  Google Scholar 

  144. Pliakas, A. M., Carlson, R. R., Neve, R. L., Konradi, C., Nestler, E. J., and Carlezon, W. A., Jr. (2001) Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J. Neurosci. 21, 7397–7403.

    PubMed  CAS  Google Scholar 

  145. Dumartin, B., Caille, I., Gonon, F., and Bloch, B. (1998) Internalization of D1 dopamine receptor in striatal neurons in vivo as evidence of activation by dopamine agonists. J. Neurosci. 18, 1650–1661.

    PubMed  CAS  Google Scholar 

  146. Zhang, X. F., Hu, X. T., and White, F. J. (1998) Whole-cell plasticity in cocaine withdrawal: reduced sodium currents in nucleus accumbens neurons. J. Neurosci. 18, 488–498.

    PubMed  Google Scholar 

  147. Volkow, N. D., Fowler, J. S., and Wang, G. J. (1999) Imaging studies on the role of dopamine in cocaine reinforcement and addiction in humans. J. Psychopharmacol. 13, 337–345.

    Article  PubMed  CAS  Google Scholar 

  148. Di Chiara, G. and Imperato, A. (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl. Acad. Sci. USA 85, 5274–5278.

    Article  PubMed  Google Scholar 

  149. Pontieri, F. E., Tanda, G., and Di Chiara, G. (1995) Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc. Natl. Acad. Sci. USA 92, 12304–12308.

    Article  PubMed  CAS  Google Scholar 

  150. Di Ciano, P., Blaha, C. D., and Phillips, A. G. (2002) Inhibition of dopamine efflux in the rat nucleus accumbens during abstinence after free access to d-amphetamine. Behav. Brain Res. 128, 1–12.

    Article  PubMed  Google Scholar 

  151. Post, R. M. (1980) Intermittent versus continuous stimulation: effect of time interval on the development of sensitization or tolerance. Life Sci. 26, 1275–1282.

    Article  PubMed  CAS  Google Scholar 

  152. Bradberry, C. W., Barrett-Larimore, R. L., Jatlow, P., and Rubino, S. R. (2000) Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys. J. Neurosci. 20, 3874–3883.

    PubMed  CAS  Google Scholar 

  153. Robbins, T. W., Mittleman, G., O’Brien, J., and Winn, P. (1990) The neuropsychological significance of stereotypy induced by stimulant drugs, in Neurobiology of Stereotyped Behavior (Cooper, S. J. and Dourish, C. T., eds.), Clarendon Press, Oxford, pp. 25–63.

    Google Scholar 

  154. Satel, S. L., Southwick, S. M., and Gawin, F. H. (1991) Clinical features of cocaine-induced paranoia. Am. J. Psychiatry 148, 495–498.

    PubMed  CAS  Google Scholar 

  155. Sato, M., Chen, C. C., Akiyama, K., and Otsuki, S. (1983) Acute exacerbation of paranoid psychotic state after long-term abstinence in patients with previous methamphetamine psychosis. Biol. Psychiatry 18, 429–440.

    PubMed  CAS  Google Scholar 

  156. Vorel, S. R., Liu, X., Hayes, R. J., Spector, J. A., and Gardner, E. L. (2001) Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292, 1175–1178.

    Article  PubMed  CAS  Google Scholar 

  157. Dennett, D. C. (1984) Elbow Room: The Varieties of Free Will Worth Wanting. Oxford University Press, New York.

    Google Scholar 

  158. Leshner, A. I. (1997) Addiction is a brain disease, and it matters. Science 278, 45–47.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Cognitive Neurobiology, Department of Psychology, Boston University, Boston, MA

    Joshua D. Berke

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  1. Joshua D. Berke
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  1. School of Pharmacy, University of Missouri-Kansas City, Kansas, USA

    John Q. Wang

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Berke, J.D. (2003). Learning and Memory Mechanisms Involved in Compulsive Drug Use and Relapse. In: Wang, J.Q. (eds) Drugs of Abuse. Methods In Molecular Medicine™, vol 79. Humana Press. https://doi.org/10.1385/1-59259-358-5:75

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  • DOI: https://doi.org/10.1385/1-59259-358-5:75

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-057-1

  • Online ISBN: 978-1-59259-358-3

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