Addiction and the brain: The neurobiology of compulsion and its persistence

Nature Reviews Neuroscience - Tập 2 Số 10 - Trang 695-703 - 2001
Steven E. Hyman1, Robert C. Malenka2
1National Institute of Mental Health, 6001 Executive Boulevard, Bethesda, Maryland 20892-9669, USA.
2Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University School of Medicine, Palo Alto, USA

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Hyman, S. E. A man with alcoholism and HIV infection. J. Am. Med. Assoc. 274, 837–843 (1995).

Hyman, S. E. Clinical crossroads. A 28 year old man addicted to cocaine. J. Am. Med. Assoc. (in the press).

O'Brien, C. P., Childress, A. R., Ehrman, R. & Robbins, S. J. Conditioning factors in drug abuse: can they explain compulsion? J. Psychopharmacol. 12, 15–22 (1998).A clear summary of the clinical correlates of classical conditioning in addiction.

Wise, R. A. & Bozarth, M. A. A psychomotor stimulant theory of addiction. Psychol. Rev. 94, 469–492 (1987).A seminal and classic conceptualization of addiction.

Wise, R. A. Addiction becomes a brain disease. Neuron 26, 27–33 (2000).

McLellan, A. T., Lewis, D. C., O'Brien, C. P. & Kleber, H. D. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcome evaluation. J. Am. Med. Assoc. 284, 1689–1695 (2000).

Hser, Y. I., Hoffman, V., Grella, C. E. & Anglin, M. D. A 33-year follow-up of narcotics addicts. Arch. Gen. Psychiatry 58, 503–508 (2001).

Nestler, E. J. Molecular basis of long-term plasticity underlying addiction. Nature Rev. Neurosci. 2, 119–128 (2001).The most up-to-date review of drug-induced molecular changes in the brain.

Berke, J. D. & Hyman, S. E. Addiction, dopamine, and the molecular mechanisms of memory. Neuron 25, 515–532 (2000).Focuses on mechanisms that can explain the compulsive use of psychostimulants (cocaine and amphetamine) and late relapse. The proposed central role of associative learning mechanisms forms a basis for the current review.

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

Kendler, K. S., Karkowski, L. M., Neale, M. C. & Prescott, C. A. Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Arch. Gen. Psychiatry 57, 261–269 (2000).

Tsuang, M. T. et al. Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. Am. J. Med. Genet. 67, 473–477 (1996).

Robinson, T. E. & Berridge, K. C. The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95, S91–117 (2000).

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

Kalivas, P. W. & Stewart, J. Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res. Brain Res. Rev. 16, 223–244 (1991).

Anagnostaras, S. G. & Robinson, T. E. Sensitization to the psychomotor stimulant effects of amphetamine: modulation by associative learning. Behav. Neurosci. 110, 1397–1414 (1996).

Badiani, A., Anagnostaras, S. G. & Robinson, T. E. The development of sensitization to the psychomotor stimulant effects of amphetamine is enhanced in a novel environment. Psychopharmacology (Berl.) 117, 443–452 (1995).

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Press, Washington DC, 1994).

Nestler, E. J. Under siege: the brain on opiates. Neuron 16, 897–900 (1996).

Markou, A. & Koob, G. F. Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacology 4, 17–26 (1991).

Weiss, F., Markou, A., Lorang, M. T. & Koob, G. F. Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res. 593, 314–318 (1992).

Williams, J. T., Christie, M. J. & Manzoni, O. Cellular and synaptic adaptations mediating opioid dependence. Physiol. Rev. 81, 299–343 (2001).

Robinson, T. E. & Berridge, K. C. The neural basis of drug craving: an incentive–sensitization theory of addiction. Brain Res. Brain Res. Rev. 18, 247–291 (1993).Sets out a model of addiction in which drugs increase the sensitivity of circuits involved in 'wanting' rather than 'liking' drugs.

O'Brien, C. P., Childress, A. R., McLellan, A. T. & Ehrman, R. Classical conditioning in drug-dependent humans. Ann. NY Acad. Sci. 654, 400–415 (1992).

Wikler, A. & Pescor, F. T. Classical conditioning of a morphine abstinence phenomenon, reinforcement of opioid-drinking behavior and “relapse” in morphine-addicted rats. Psychopharmacologia 10, 255–284 (1967).

Kelley, A. E., Smith-Roe, S. L. & Holahan, M. R. Response-reinforcement learning is dependent on N-methyl-d-aspartate receptor activation in the nucleus accumbens core. Proc. Natl Acad. Sci. USA 94, 12174–12179 (1997).

Ciccocioppo, R., Sanna, P. P. & Weiss, F. Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D1 antagonists. Proc. Natl Acad. Sci. USA 98, 1976–1981 (2001).

Stewart, J., De Wit, H. & Eikelboom, R. Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol. Rev. 91, 251–268 (1984).

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

Robinson, T. E., Becker, J. B. & Presty, S. K. Long-term facilitation of amphetamine-induced rotational behavior and striatal dopamine release produced by a single exposure to amphetamine: sex differences. Brain Res. 253, 231–241 (1982).

Robinson, T. E. & Becker, J. B. Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res. 396, 157–198 (1986).

Piazza, P. V. & Le Moal, M. L. Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons. Annu. Rev. Pharmacol. Toxicol. 36, 359–378 (1996).An exposition of the role of stress and stress hormones in drug abuse; complementary to the content of this review.

Ehrman, R. N., Robbins, S. J., Childress, A. R. & O'Brien, C. P. Conditioned responses to cocaine-related stimuli in cocaine abuse patients. Psychopharmacology (Berl.) 107, 523–529 (1992).

Grant, S. et al. Activation of memory circuits during cue-elicited cocaine craving. Proc. Natl Acad. Sci. USA 93, 12040–12045 (1996).

Childress, A. R. et al. Limbic activation during cue-induced cocaine craving. Am. J. Psychiatry 156, 11–18 (1999).

Kilts, C. D. et al. Neural activity related to drug craving in cocaine addiction. Arch. Gen. Psychiatry 58, 334–341 (2001).

Maas, L. C. et al. Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving. Am. J. Psychiatry 155, 124–126 (1998).

Everitt, B. J., Morris, K. A., O'Brien, A. & Robbins, T. W. The basolateral amygdala–ventral striatal system and conditioned place preference: further evidence of limbic–striatal interactions underlying reward-related processes. Neuroscience 42, 1–18 (1991).

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

Di Chiara, G. & Imperato, A. 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 (1988).

Wise, R. A. Addictive drugs and brain stimulation reward. Annu. Rev. Neurosci. 19, 319–340 (1996).

Robbins, T. W. & Everitt, B. J. Neurobehavioural mechanisms of reward and motivation. Curr. Opin. Neurobiol. 6, 228–236 (1996).

Koob, G. F. & Bloom, F. E. Cellular and molecular mechanisms of drug dependence. Science 242, 715–723 (1988).

Johnson, S. W. & North, R. A. Opioids excite dopamine neurons by hyperpolarization of local interneurons. J. Neurosci. 12, 483–488 (1992).

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

Breiter, H. C. et al. Acute effects of cocaine on human brain activity and emotion. Neuron 19, 591–611 (1997).The first study convincingly to show activation of brain reward circuitry in humans by cocaine.

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

Waelti, P., Dickinson, A. & Schultz, W. Dopamine responses comply with basic assumptions of formal learning theory. Nature 412, 43–48 (2001).The most recent of a series of papers by Schultz and colleagues, arguing that dopamine serves as a learning signal.

Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science 275, 1593–1599 (1997).

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

Kalivas, P. W. Interactions between dopamine and excitatory amino acids in behavioral sensitization to psychostimulants. Drug Alcohol Depend. 37, 95–100 (1995).

Hu, X. T. & White, F. J. Dopamine enhances glutamate-induced excitation of rat striatal neurons by cooperative activation of D1 and D2 class receptors. Neurosci. Lett. 224, 61–65 (1997).

Wolf, M. E. The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog. Neurobiol. 54, 679–720 (1998).

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

Bear, M. F. Progress in understanding NMDA-receptor-dependent synaptic plasticity in the visual cortex. J. Physiol. (Paris) 90, 223–227 (1996).

Clark, D. & Overton, P. G. Alterations in excitatory amino acid-mediated regulation of midbrain dopaminergic neurons induced by chronic psychostimulant administration and stress: relevance to behavioral sensitization and drug addiction. Addict. Biol. 3, 109–135 (1998).

Malenka, R. C. Synaptic plasticity in the hippocampus: LTP and LTD. Cell 78, 535–538 (1994).

Malenka, R. C. & Nicoll, R. A. Long-term potentiation — a decade of progress? Science 285, 1870–1874 (1999).An up-to-date review of current thinking about LTP in the hippocampus.

Pennartz, C. M., Ameerun, R. F., Groenewegen, H. J. & Lopes da Silva, F. H. Synaptic plasticity in an in vitro slice preparation of the rat nucleus accumbens. Eur. J. Neurosci. 5, 107–117 (1993).

Kombian, S. B. & Malenka, R. C. Simultaneous LTP of non-NMDA- and LTD of NMDA-receptor-mediated responses in the nucleus accumbens. Nature 368, 242–246 (1994).

Thomas, M. J., Malenka, R. C. & Bonci, A. Modulation of long-term depression by dopamine in the mesolimbic system. J. Neurosci. 20, 5581–5586 (2000).

Li, Y. & Kauer, J. A. Amphetamine interferes with long-term potentiation in the nucleus accumbens. Soc. Neurosci. Abstr. 26, 1398 (2000).

Nicola, S. M., Surmeier, J. & Malenka, R. C. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu. Rev. Neurosci. 23, 185–215 (2000).Reviews the actions of dopamine on neuronal excitability and synaptic transmission in the striatum.

Calabresi, P., Centonze, D. & Bernardi, G. Electrophysiology of dopamine in normal and denervated striatal neurons. Trends Neurosci. 23, S57–63 (2000).

Calabresi, P., Pisani, A., Mercuri, N. B. & Bernardi, G. The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia. Trends Neurosci. 19, 19–24 (1996).

Choi, S. & Lovinger, D. M. Decreased probability of neurotransmitter release underlies striatal long-term depression and postnatal development of corticostriatal synapses. Proc. Natl Acad. Sci. USA 94, 2665–2670 (1997).

Bonci, A. & Malenka, R. C. Properties and plasticity of excitatory synapses on dopaminergic and GABAergic cells in the ventral tegmental area. J. Neurosci. 19, 3723–3730 (1999).

Jones, S., Kornblum, J. L. & Kauer, J. A. Amphetamine blocks long-term synaptic depression in the ventral tegmental area. J. Neurosci. 20, 5575–5580 (2000).These two papers describe the basic properties of LTP and LTD in the VTA.

Kornblum, J. L. & Kauer, J. A. Long-term depression (LTD) in the ventral tegmental area (VTA) requires cyclic AMP dependent protein kinase (PKA). Soc. Neurosci. Abstr. (in the press).

Ungless, M. A., Whisler, J. L., Malenka, R. C. & Bonci, A. Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411, 583–587 (2001).This paper demonstrates that in vivo cocaine administration causes LTP at excitatory synapses in the VTA.

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

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

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

Thomas, M. J. & Malenka, R. C. Behavioral sensitization to cocaine is associated with changes in nucleus accumbens synaptic transmission. Soc. Neurosci. Abstr. 26, 791 (2000).

Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory storage. Annu. Rev. Physiol. 55, 397–426 (1993).

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

Geinisman, Y., Berry, R. W., Disterhoft, J. F., Power, J. M. & Van der Zee, E. A. Associative learning elicits the formation of multiple-synapse boutons. J. Neurosci. 21, 5568–5573 (2001).

Ingham, C. A., Hood, S. H. & Arbuthnott, G. W. Spine density on neostriatal neurones changes with 6-hydroxydopamine lesions and with age. Brain Res. 503, 334–338 (1989).

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

Meredith, G. E., Ypma, P. & Zahm, D. S. 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 (1995).

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

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

Robinson, T. E. & Kolb, B. 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 (1999).These two papers show that the chronic in vivo administration of psychostimulants changes the morphology of dendritic spines in the nucleus accumbens and prefrontal cortex.

Hope, B. T. et al. Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments. Neuron 13, 1235–1244 (1994).

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

Kuhar, M. J., Joyce, A. & Dominguez, G. Genes in drug abuse. Drug Alcohol Depend. 62, 157–162 (2001).

Kelz, M. B. et al. Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine. Nature 401, 272–276 (1999).

Bibb, J. A. et al. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410, 376–380 (2001).

Shaywitz, A. J. & Greenberg, M. E. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 68, 821–861 (1999).

Bourtchuladze, R. et al. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79, 59–68 (1994).

Yin, J. C. et al. Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79, 49–58 (1994).

Nguyen, P. V., Abel, T. & Kandel, E. R. Requirement of a critical period of transcription for induction of a late phase of LTP. Science 265, 1104–1107 (1994).

Frey, U., Frey, S., Schollmeier, F. & Krug, M. Influence of actinomycin D, an RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro. J. Physiol. (Lond.) 490, 703–711 (1996).

Nguyen, P. V. & Kandel, E. R. A macromolecular synthesis-dependent late phase of long-term potentiation requiring cAMP in the medial perforant pathway of rat hippocampal slices. J. Neurosci. 16, 3189–3198 (1996).

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

Das, S., Grunert, M., Williams, L. & Vincent, S. R. NMDA and D1 receptors regulate the phosphorylation of CREB and the induction of c-fos in striatal neurons in primary culture. Synapse 25, 227–233 (1997).

Konradi, C., Leveque, J. C. & Hyman, S. E. Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium. J. Neurosci. 16, 4231–4239 (1996).

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

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

Spanagel, R., Herz, A. & Shippenberg, T. S. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl Acad. Sci. USA 89, 2046–2050 (1992).

Steiner, H. & Gerfen, C. R. Dynorphin regulates D1 dopamine receptor-mediated responses in the striatum: relative contributions of pre- and postsynaptic mechanisms in dorsal and ventral striatum demonstrated by altered immediate-early gene induction. J. Comp Neurol. 376, 530–541 (1996).

Shippenberg, T. S., Bals-Kubik, R. & Herz, A. Examination of the neurochemical substrates mediating the motivational effects of opioids: role of the mesolimbic dopamine system and D-1 vs. D-2 dopamine receptors. J. Pharmacol. Exp. Ther. 265, 53–59 (1993).

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

Carlezon, W. A. Jr et al. Regulation of cocaine reward by CREB. Science 282, 2272–2275 (1998).

Spangler, R. et al. Regulation of κ opioid receptor mRNA in the rat brain by 'binge' pattern cocaine administration and correlation with preprodynorphin mRNA. Brain Res. Mol. Brain Res. 38, 71–76 (1996).

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

Simpson, J. N., Wang, J. Q. & McGinty, J. F. Repeated amphetamine administration induces a prolonged augmentation of phosphorylated cyclase response element-binding protein and Fos-related antigen immunoreactivity in rat striatum. Neuroscience 69, 441–457 (1995).

Lyford, G. L. et al. Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron 14, 433–445 (1995).

Cole, A. J., Saffen, D. W., Baraban, J. M. & Worley, P. F. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340, 474–476 (1989).

O'Brien, R. J. et al. Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23, 309–323 (1999).

Yamagata, K. et al. Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268. Learn. Mem. 1, 140–152 (1994).

Berridge, K. C. & Robinson, T. E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res. Brain Res. Rev. 28, 309–369 (1998).