Drug Addiction, Dysregulation of Reward, and Allostasis
Abstract
This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drug-taking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hedonic dysregulation underlies addiction, stress, and chronic pain, as shown by a shift in the relative salience of natural reward to drug reward in people with severe substance use disorders.
“Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders.”
Negative affective symptoms of withdrawal act as negative reinforcers that sustain addiction.
“The emergence of negative affective symptoms, such as dysphoria, anxiety and irritability and, to a lesser extent, the somatic manifestations of withdrawal, serve as negative reinforcers that sustain the vicious cycle of addiction [23, 121, 132–134].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [132]
Allostatic theory asserts reward insensitivity and negative reinforcement underlie the later and more severe stages of addiction.
“but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
Allostatic theory asserts heightened brain reward sensitivity and positive reinforcement characterize the early stages of addiction.
“Finally, allostatic theory asserts heightened brain reward sensitivity and positive reinforcement characterize the early stages of addiction(18), but reward insensitivity and negative reinforcement underlie the later and more severe stages(18–20).”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
The reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol.
“Limitations included that the reexamination interval may not have been sufficient to observe the extent of neuroadaptative responses to alcohol(18)”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [18]
Cites
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370 · see citing works
Protective and Damaging Effects of Stress Mediators
McEwen, B. S. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801153380307 · Cited by 6,733 · cited 3× · see citing works
“Different types of allostatic load have been considered that may explain different types or gradients of morbidity (McEwen 1998a).”
BackgroundCellular and molecular mechanisms of drug dependence
Koob, G. F., & Bloom, F. E. (1988) · Science · doi:10.1126/science.2903550 · Cited by 2,070 · see citing works
Self-citation(1997) · Journal of Studies on Alcohol · doi:10.15288/jsa.1997.58.7 · Cited by 1,905 · see citing works
Matthes, H. W. D., Maldonado, R., Simonin, F., Valverde, O., Slowe, S., Kitchen, I., Befort, K., Dierich, A., Le Meur, M., Dollé, P., et al. (1996) · Nature · doi:10.1038/383819a0 · Cited by 1,722 · see citing works
An opponent-process theory of motivation. I. Temporal dynamics of affect
Solomon, R. L., & Corbit, J. D. (1974) · Psychological Review · doi:10.1037/h0036128 · Cited by 1,704 · see citing works
Baxter, L. R. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820090009002 · Cited by 1,293 · see citing works
Alheid, G. F., & Heimer, L. (1988) · Neuroscience · doi:10.1016/0306-4522(88)90217-5 · Cited by 1,217 · see citing works
Koob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026 · see citing works
Self-citationActivation of memory circuits during cue-elicited cocaine craving.
Grant, S., London, E. D., Newlin, D. B., Villemagne, V. L., Liu, X., Contoreggi, C., Phillips, R. L., Kimes, A. S., & Margolin, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.12040 · Cited by 936 · see citing works
Alcohol problems in adoptees raised apart from alcoholic biological parents
Goodwin, D. W. (1973) · Archives of General Psychiatry · doi:10.1001/archpsyc.1973.01750320068011 · Cited by 882 · see citing works
The mesolimbic dopaminergic system is implicated in the reinforcing effects of nicotine
Corrigall, W. A., Franklin, K. B. J., Coen, K. M., & Clarke, P. B. S. (1992) · Psychopharmacology · doi:10.1007/bf02245149 · Cited by 829 · see citing works
Familial Transmission of Substance Use Disorders
Merikangas, K. R., Stolar, M., Stevens, D. E., Goulet, J., Preisig, M. A., Fenton, B., Zhang, H., O'Malley, S. S., & Rounsaville, B. J. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.11.973 · Cited by 783 · see citing works
Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems
EVERITT, B. J., PARKINSON, J. A., OLMSTEAD, M. C., ARROYO, M., ROBLEDO, P., & ROBBINS, T. W. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb09280.x · Cited by 708 · cited 5× · see citing works
“In contrast, the ventral subiculum appears to mediate the potentiation of locomotor activation and conditioned reinforcement by stimulant drugs but does not mediate informational aspects of the conditioned reinforcement process (Everitt et al. 1999).”
BackgroundInfluentialPettit, H. O., Ettenberg, A., Bloom, F. E., & Koob, G. F. (1984) · Psychopharmacology · doi:10.1007/bf00427441 · Cited by 651 · see citing works
Self-citationHeroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems
Ettenberg, A., Pettit, H. O., Bloom, F. E., & Koob, G. F. (1982) · Psychopharmacology · doi:10.1007/bf00428151 · Cited by 563 · see citing works
Self-citationActivation of Corticotropin-Releasing Factor in the Limbic System During Cannabinoid Withdrawal
Rodrı́guez de Fonseca, F., Carrera, M. R. A., Navarro, M., Koob, G. F., & Weiss, F. (1997) · Science · doi:10.1126/science.276.5321.2050 · Cited by 499 · see citing works
Self-citationWeiss, F., Parsons, L. H., Schulteis, G., Hyytiä, P., Lorang, M. T., Bloom, F. E., & Koob, G. F. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-10-03474.1996 · Cited by 457 · see citing works
Self-citationRassnick, S., Heinrichs, S. C., Britton, K. T., & Koob, G. F. (1993) · Brain Research · doi:10.1016/0006-8993(93)91352-s · Cited by 407 · see citing works
Self-citationAllostasis, amygdala, and anticipatory angst
Schulkin, J., McEwen, B. S., & Gold, P. W. (1994) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(94)90051-5 · Cited by 380 · see citing works
Stinus, L., Le Moal, M., & Koob, G. F. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90106-e · Cited by 317 · see citing works
Self-citationShaham, Y., Erb, S., Leung, S., Buczek, Y., & Stewart, J. (1998) · Psychopharmacology · doi:10.1007/s002130050608 · Cited by 302 · see citing works
Synaptic regulation of mesocorticolimbic dopamine neurons
White, F. J. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.19.030196.002201 · Cited by 289 · see citing works
The Amygdala: Corticotropin-Releasing Factor, Steroids, and Stress
Gray, T. S., & Bingaman, E. W. (1996) · Critical Reviews™ in Neurobiology · doi:10.1615/critrevneurobiol.v10.i2.10 · Cited by 230 · see citing works
Homeostatic theory of drug tolerance: a general model of physiological adaptation
Poulos, C. X., & Cappell, H. (1991) · Psychological Review · doi:10.1037/0033-295x.98.3.390 · Cited by 221 · see citing works
The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent
Barrot, M., Marinelli, M., Abrous, D. N., Rougé‐Pont, F., Le Moal, M., & Piazza, P. V. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00996.x · Cited by 210 · see citing works
Evidence for opiate-activated NMDA processes masking opiate analgesia in rats
Célèrier, E., Laulin, J.-P., Larcher, A., Le Moal, M., & Simonnet, G. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01998-8 · Cited by 182 · see citing works
Laulin, J. P., Célèrier, E., Larcher, A., Le Moal, M., & Simonnet, G. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00652-6 · Cited by 179 · see citing works
Experimental approach to individual vulnerability to psychostimulant addiction
Deminiere, J. M., Piazza, P. V., Le Moal, M., & Simon, H. (1989) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(89)80023-5 · Cited by 177 · see citing works
Long-lasting increased pain sensitivity in rat following exposure to heroin for the first time
Laulin, J., Larcher, A., Célèrier, E., Moal, M. L., & Simonnet, G. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00083.x · Cited by 156 · cited 1× · see citing works
“This hyperalgesia can be blocked by noncompetitive NMDA receptor antagonists suggesting a critical role for glutamatergic systems (Celerier et al. 1999; Larcher et al. 1998; Laulin et al. 1998).”
BackgroundReceptor subtype-specific dopaminergic agents and conditioned behavior
Beninger, R. J., Hoffman, D. C., & Mazurski, E. J. (1989) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(89)80019-3 · Cited by 109 · see citing works
Kreek, M., Ragunath, J., Plevy, S., Hamer, D., Schneider, B., & Hartman, N. (1984) · Neuropeptides · doi:10.1016/0143-4179(84)90081-7 · Cited by 97 · see citing works
Corticotropin-releasing factor induces a place aversion independent of its neuroendocrine role
Cador, M., Ahmed, S. H., Koob, G. F., Le Moal, M., & Stinus, L. (1992) · Brain Research · doi:10.1016/0006-8993(92)91487-y · Cited by 74 · see citing works
Self-citationMacey, D. J., Koob, G. F., & Markou, A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02229-0 · Cited by 69 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Koob, G. F., & Volkow, N. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.110 · Cited by 5,340 · see citing works
Self-citationNeural systems of reinforcement for drug addiction: from actions to habits to compulsion
Everitt, B. J., & Robbins, T. W. (2005) · Nature Neuroscience · doi:10.1038/nn1579 · Cited by 3,785 · see citing works
Neurobiology of addiction: a neurocircuitry analysis
Koob, G. F., & Volkow, N. D. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)00104-8 · Cited by 3,698 · see citing works
Self-citationThe concept of allostasis in biology and biomedicine
McEwen, B. S., & Wingfield, J. C. (2003) · Hormones and Behavior · doi:10.1016/s0018-506x(02)00024-7 · Cited by 3,302 · see citing works
Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications
Goldstein, R. Z., & Volkow, N. D. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3119 · Cited by 2,749 · see citing works
The Neural Basis of Addiction: A Pathology of Motivation and Choice
Kalivas, P. W., & Volkow, N. D. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.8.1403 · Cited by 2,757 · see citing works
Goldstein, R. Z., & Volkow, N. D. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.10.1642 · Cited by 2,667 · see citing works
The mesolimbic dopamine reward circuit in depression
Nestler, E. J., & Carlezon, W. A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.09.018 · Cited by 2,059 · see citing works
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957 · see citing works
MCEWEN, B. S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1314.001 · Cited by 1,638 · see citing works
Stress revisited: a critical evaluation of the stress concept
Koolhaas, J. M., Bartolomucci, A., Buwalda, B., de Boer, S. F., Flügge, G., Korte, S. M., Meerlo, P., Murison, R., Olivier, B., Palanza, P., et al. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.02.003 · Cited by 1,626 · see citing works
Comorbidity: a network perspective
Cramer, A. O. J., Waldorp, L. J., van der Maas, H. L. J., & Borsboom, D. (2010) · Behavioral and Brain Sciences · doi:10.1017/s0140525x09991567 · Cited by 1,575 · see citing works
Robinson, T. E., & Berridge, K. C. (2003) · Annual Review of Psychology · doi:10.1146/annurev.psych.54.101601.145237 · Cited by 1,509 · see citing works
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477 · see citing works
Addiction and the brain antireward system
Koob, G. F., & Le Moal, M. (2008) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093548 · Cited by 1,457 · see citing works
Self-citationIs there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388 · see citing works
Motivation concepts in behavioral neuroscience
Berridge, K. C. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.02.004 · Cited by 1,302 · see citing works
The genetics of addictions: uncovering the genes
Goldman, D., Oroszi, G., & Ducci, F. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1635 · Cited by 1,099 · see citing works
Korte, S. M., Koolhaas, J. M., Wingfield, J. C., & McEwen, B. S. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.08.009 · Cited by 1,097 · see citing works
Allostasis: A model of predictive regulation
Sterling, P. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.06.004 · Cited by 1,073 · see citing works
A Role for Brain Stress Systems in Addiction
Koob, G. F. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.012 · Cited by 1,056 · see citing works
Self-citationReward Processing by the Opioid System in the Brain
Le Merrer, J., Becker, J. A. J., Befort, K., & Kieffer, B. L. (2009) · Physiological Reviews · doi:10.1152/physrev.00005.2009 · Cited by 1,013 · see citing works
High Impulsivity Predicts the Switch to Compulsive Cocaine-Taking
Belin, D., Mar, A. C., Dalley, J. W., Robbins, T. W., & Everitt, B. J. (2008) · Science · doi:10.1126/science.1158136 · Cited by 989 · see citing works
Nucleus accumbens shell and core dopamine: differential role in behavior and addiction
Di Chiara, G. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(02)00286-3 · Cited by 996 · see citing works
Everitt, B. J., Belin, D., Economidou, D., Pelloux, Y., Dalley, J. W., & Robbins, T. W. (2008) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2008.0089 · Cited by 974 · see citing works
Adult neurogenesis: from precursors to network and physiology
Abrous, D. N., Koehl, M., & Le Moal, M. (2005) · Physiological Reviews · doi:10.1152/physrev.00055.2003 · Cited by 971 · see citing works
The role of impulsivity in the development of substance use and eating disorders
Dawe, S., & Loxton, N. J. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.007 · Cited by 944 · see citing works
Neurobiology of relapse to heroin and cocaine seeking: a review
Shalev, U., Grimm, J. W., & Shaham, Y. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.1.1 · Cited by 880 · see citing works
Wise, R. A. (2002) · Neuron · doi:10.1016/s0896-6273(02)00965-0 · Cited by 881 · see citing works
The addicted human brain: insights from imaging studies
Volkow, N. D., Fowler, J. S., & Wang, G.-J. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18533 · Cited by 916 · see citing works
Stress dysregulation of drug reward pathways, and the transition to drug dependence
Koob, & Kreek, M. J. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.05030503 · Cited by 868 · see citing works
Garland, E. L., Farb, N. A., R. Goldin, P., & Fredrickson, B. L. (2015) · Psychological Inquiry · doi:10.1080/1047840x.2015.1064294 · Cited by 810 · see citing works
The neuropsychological basis of addictive behaviour
Everitt, B. J., Dickinson, A., & Robbins, T. W. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00088-1 · Cited by 808 · see citing works
The role of impulsive behavior in drug abuse
Perry, J. L., & Carroll, M. E. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1173-0 · Cited by 805 · see citing works
Sex, stress and the hippocampus: allostasis, allostatic load and the aging process
MCEWEN, B. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00027-1 · Cited by 753 · see citing works
Dopamine system dysregulation in major depressive disorders
Belujon, P., & Grace, A. A. (2017) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyx056 · Cited by 754 · see citing works
Sex Differences in Animal Models: Focus on Addiction
Becker, J. B., & Koob, G. F. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011163 · Cited by 725 · see citing works
Self-citationLimbic-frontal circuitry in major depression: a path modeling metanalysis
Seminowicz, D. A., Mayberg, H. S., McIntosh, A. R., Goldapple, K., Kennedy, S., Segal, Z., & Rafi-Tari, S. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.01.015 · Cited by 710 · see citing works
Distinct extended amygdala circuits for divergent motivational states
Jennings, J. H., Sparta, D. R., Stamatakis, A. M., Ung, R. L., Pleil, K. E., Kash, T. L., & Stuber, G. D. (2013) · Nature · doi:10.1038/nature12041 · Cited by 704 · see citing works
“Recorded vBNST units were classified as light-responsive, and thus VTA-projecting, if they met both of the following two criteria: (1) the latency of the first spike after light stimulation onset was less than 20ms for$20% of the trials; and (2) light-evoked and spontaneous waveform shapes had a correlation coefficien…”
BackgroundMethodWaldhoer, M., Bartlett, S. E., & Whistler, J. L. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073940 · Cited by 740 · see citing works
Streeter, C. C., Gerbarg, P. L., Saper, R. B., Ciraulo, D. A., & Brown, R. P. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.01.021 · Cited by 694 · see citing works
Psychomotor stimulant addiction: a neural systems perspective
Everitt, B. J., & Wolf, M. E. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03312.2002 · Cited by 700 · see citing works
Chronic stress and comfort foods: Self-medication and abdominal obesity
Dallman, M. F., Pecoraro, N. C., & la Fleur, S. E. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.11.004 · Cited by 656 · see citing works
Aldao, A., Gee, D. G., De Los Reyes, A., & Seager, I. (2016) · Development and Psychopathology · doi:10.1017/s0954579416000638 · Cited by 636 · see citing works
Strang, J., Volkow, N. D., Degenhardt, L., Hickman, M., Johnson, K., Koob, G. F., Marshall, B. D. L., Tyndall, M., & Walsh, S. L. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0137-5 · Cited by 639 · see citing works
Self-citationThe insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making
Naqvi, N. H., & Bechara, A. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0268-7 · Cited by 598 · see citing works
Stressed or Stressed out: What Is the Difference?
McEwen, B. S. (2005) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0540 · Cited by 593 · see citing works
Hyperdopaminergic mutant mice have higher "wanting" but not "liking" for sweet rewards
Peciña, S., Cagniard, B., Berridge, K. C., Aldridge, J. W., & Zhuang, X. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09395.2003 · Cited by 551 · see citing works
Neurobiologic processes in drug reward and addiction
Adinoff, B. (2004) · Harvard Review of Psychiatry · doi:10.1080/10673220490910844 · Cited by 546 · see citing works
Belin, D., Jonkman, S., Dickinson, A., Robbins, T. W., & Everitt, B. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.09.027 · Cited by 520 · see citing works
Barrot, M., Olivier, J. D. A., Perrotti, L. I., DiLeone, R. J., Berton, O., Eisch, A. J., Impey, S., Storm, D. R., Neve, R. L., Yin, J. C., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172091899 · Cited by 508 · see citing works
Pliakas, A. M., Carlson, R. R., Neve, R. L., Konradi, C., Nestler, E. J., & Carlezon, W. A. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-18-07397.2001 · Cited by 509 · see citing works
A key role for corticotropin-releasing factor in alcohol dependence
Heilig, M., & Koob, G. F. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.006 · Cited by 503 · see citing works
Self-citationThe neurobiology of opioid dependence: implications for treatment
Kosten, T., & George, T. (2002) · Science & Practice Perspectives · doi:10.1151/spp021113 · Cited by 505 · see citing works
Addiction as a stress surfeit disorder
Koob, G. F., Buck, C. L., Cohen, A., Edwards, S., Park, P. E., Schlosburg, J. E., Schmeichel, B., Vendruscolo, L. F., Wade, C. L., Whitfield, T. W., et al. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.05.024 · Cited by 483 · see citing works
Self-citationIt could be habit forming: drugs of abuse and striatal synaptic plasticity
Gerdeman, G. L., Partridge, J. G., Lupica, C. R., & Lovinger, D. M. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00065-1 · Cited by 480 · see citing works
Camí, J., & Farré, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023160 · Cited by 477 · see citing works
Neurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477 · see citing works
Self-citationExcessive sugar intake alters binding to dopamine and mu-opioid receptors in the brain
Colantuoni, C., Schwenker, J., McCarthy, J., Rada, P., Ladenheim, B., Cadet, J.-L., Schwartz, G. J., Moran, T. H., & Hoebel, B. G. (2001) · Neuroreport · doi:10.1097/00001756-200111160-00035 · Cited by 471 · see citing works
Sensitive periods of substance abuse: Early risk for the transition to dependence
Jordan, C. J., & Andersen, S. L. (2017) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2016.10.004 · Cited by 455 · see citing works
REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?
Heilig, M., Egli, M., Crabbe, J. C., & Becker, H. C. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2009.00194.x · Cited by 435 · see citing works
The dark side of emotion: the addiction perspective
Koob, G. F. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.11.044 · Cited by 433 · see citing works
Self-citationWyvell, C. L., & Berridge, K. C. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07831.2001 · Cited by 436 · see citing works
Is social attachment an addictive disorder?
Insel, T. R. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00148-3 · Cited by 430 · see citing works
The neurocircuitry of addiction: an overview
Feltenstein, M. W., & See, R. E. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.51 · Cited by 421 · see citing works
Addictions neuroclinical assessment: a neuroscience-based framework for addictive disorders
Kwako, L. E., Momenan, R., Litten, R. Z., Koob, G. F., & Goldman, D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.024 · Cited by 395 · see citing works
Self-citationPharmacological evidence for a motivational role of κ-opioid systems in ethanol dependence
Walker, B. M., & Koob, G. F. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301438 · Cited by 392 · see citing works
Self-citationThe neurobiology of addiction: a neuroadaptational view relevant for diagnosis
Koob, G. F. (2006) · Addiction · doi:10.1111/j.1360-0443.2006.01586.x · Cited by 397 · see citing works
Self-citationDoremus-Fitzwater, T. L., Varlinskaya, E. I., & Spear, L. P. (2010) · Brain and Cognition · doi:10.1016/j.bandc.2009.08.008 · Cited by 397 · see citing works
Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies
Engelmann, J. M., Versace, F., Robinson, J. D., Minnix, J. A., Lam, C. Y., Cui, Y., Brown, V. L., & Cinciripini, P. M. (2012) · NeuroImage · doi:10.1016/j.neuroimage.2011.12.024 · Cited by 394 · see citing works
Addiction is a Reward Deficit and Stress Surfeit Disorder
Koob, G. F. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00072 · Cited by 397 · see citing works
Self-citationBerking, M., Margraf, M., Ebert, D., Wupperman, P., Hofmann, S. G., & Junghanns, K. (2011) · Journal of Consulting and Clinical Psychology · doi:10.1037/a0023421 · Cited by 395 · see citing works
The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration
Lightman, S. L., & Conway-Campbell, B. L. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2914 · Cited by 390 · see citing works
Atzil, S., Gao, W., Fradkin, I., & Barrett, L. F. (2018) · Nature Human Behaviour · doi:10.1038/s41562-018-0384-6 · Cited by 415 · see citing works
Chaiton, M. O., Cohen, J. E., O'Loughlin, J., & Rehm, J. (2009) · BMC Public Health · doi:10.1186/1471-2458-9-356 · Cited by 391 · see citing works
Neurobiological evidence for hedonic allostasis associated with escalating cocaine use
Ahmed, S. H., Kenny, P. J., Koob, G. F., & Markou, A. (2002) · Nature Neuroscience · doi:10.1038/nn872 · Cited by 389 · see citing works
Self-citationBrain stress systems in the amygdala and addiction
Koob, G. F. (2009) · Brain Research · doi:10.1016/j.brainres.2009.03.038 · Cited by 388 · see citing works
Self-citationRedish, A. D., Jensen, S., Johnson, A., & Kurth-Nelson, Z. (2007) · Psychological Review · doi:10.1037/0033-295x.114.3.784 · Cited by 346 · see citing works
Franken, I. H. A., Rassin, E., & Muris, P. (2007) · Journal of Affective Disorders · doi:10.1016/j.jad.2006.08.020 · Cited by 373 · see citing works
Reward, addiction, withdrawal to nicotine
De Biasi, M., & Dani, J. A. (2011) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-061010-113734 · Cited by 366 · see citing works
Corticotropin-Releasing Factor in Brain: A Role in Activation, Arousal, and Affect Regulation
Heinrichs, S. C., & Koob, G. F. (2004) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.052092 · Cited by 353 · see citing works
Self-citationSterling, P. (2004) · Allostasis, Homeostasis, and the Costs of Physiological Adaptation · doi:10.1017/cbo9781316257081.004 · Cited by 353 · see citing works
Kelley, A. E., Baldo, B. A., & Pratt, W. E. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20769 · Cited by 352 · see citing works
The insula: a critical neural substrate for craving and drug seeking under conflict and risk
Naqvi, N. H., Gaznick, N., Tranel, D., & Bechara, A. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12415 · Cited by 336 · see citing works
Alcohol dependence as a chronic pain disorder
Egli, M., Koob, G. F., & Edwards, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.010 · Cited by 347 · see citing works
Self-citationStress-related factors in cannabis use and misuse: Implications for prevention and treatment
Hyman, S. M., & Sinha, R. (2009) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2008.08.005 · Cited by 344 · see citing works
Tremblay, L. K., Naranjo, C. A., Graham, S. J., Herrmann, N., Mayberg, H. S., Hevenor, S., & Busto, U. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1228 · Cited by 340 · see citing works
A new animal welfare concept based on allostasis
Korte, S. M., Olivier, B., & Koolhaas, J. M. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.10.018 · Cited by 340 · see citing works
Natural rewards, neuroplasticity, and non-drug addictions
Olsen, C. M. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.03.010 · Cited by 339 · see citing works
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337 · see citing works
Self-citationMindfulness-Based Relapse Prevention for substance craving
Witkiewitz, K., Bowen, S., Douglas, H., & Hsu, S. H. (2013) · Addictive Behaviors · doi:10.1016/j.addbeh.2012.04.001 · Cited by 337 · see citing works
Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats
Vendruscolo, L. F., Barbier, E., Schlosburg, J. E., Misra, K. K., Whitfield, T. W., Logrip, M. L., Rivier, C., Repunte-Canonigo, V., Zorrilla, E. P., Sanna, P. P., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0069-12.2012 · Cited by 319 · see citing works
Self-citationTaylor, A. H., Ussher, M. H., & Faulkner, G. (2007) · Addiction · doi:10.1111/j.1360-0443.2006.01739.x · Cited by 324 · see citing works
Everitt, B. J. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12644 · Cited by 318 · see citing works
Stress‐Induced and Alcohol Cue‐Induced Craving in Recently Abstinent Alcohol‐Dependent Individuals
Fox, H. C., Bergquist, K. L., Hong, K., & Sinha, R. (2007) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00320.x · Cited by 315 · see citing works
Addiction and Stress: An Allostatic View
Koob, G. F., & Schulkin, J. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.008 · Cited by 315 · see citing works
Self-citationPathological gambling: a comprehensive review of biobehavioral findings
Goudriaan, A. E., Oosterlaan, J., de Beurs, E., & Van den Brink, W. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.03.001 · Cited by 313 · see citing works
Roberto, M., Schweitzer, P., Madamba, S. G., Stouffer, D. G., Parsons, L. H., & Siggins, G. R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5077-03.2004 · Cited by 312 · see citing works
Common brain mechanisms of chronic pain and addiction
Elman, I., & Borsook, D. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.027 · Cited by 303 · see citing works
The role of affective dysregulation in drug addiction
Cheetham, A., Allen, N. B., Yücel, M., & Lubman, D. I. (2010) · Clinical Psychology Review · doi:10.1016/j.cpr.2010.04.005 · Cited by 308 · see citing works
- Authors
- Koob, G.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Koob, G
- Venue
- Neuropsychopharmacology
- Published
- 2001-02
- Volume
- 24
- Issue
- 2
- Pages
- 97-129
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W1989416066
- Cited by
- 2,953
- References
- 34
- Citations by year
- 2026: 72 · 2025: 94 · 2024: 73 · 2023: 105 · 2022: 85 · 2021: 136 · 2020: 162 · 2019: 124 · 2018: 118 · 2017: 139 · 2016: 130 · 2015: 148 · 2014: 141 · 2013: 140 · 2012: 140
- FWCI
- 7.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut Universitaire de France
- National Institutes of Health (AA06420, AA08459, DK-26741)
- National Institute on Alcohol Abuse and Alcoholism (AA-06420, AA-08459)
- National Institute on Drug Abuse (DA04043, AA06420, R01DA004043)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 26741)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- drug addiction, allostasis, relapse vulnerability, opponent process theory, stress response, compulsive drug taking, neural adaptation, homeostasis
- MeSH terms
- Animals, Humans, Hypothalamo-Hypophyseal System, Models, Neurological, Nerve Net, Pituitary-Adrenal System, Reinforcement, Psychology, Reward, Stress, Physiological, Substance Withdrawal Syndrome, Temperance, Behavior, Addictive, Substance-Related Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
