Abstract
Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Robison, A. J. & Nestler, E. J. Transcriptional and epigenetic mechanisms of addiction. Nat. Rev. Neurosci. 12, 623–637 (2011).
Koob, G. F. & Le Moal, M. Addiction and the brain antireward system. Annu. Rev. Psychol. 59, 29–53 (2008).
Wise, R. A. Dopamine, learning and motivation. Nat. Rev. Neurosci. 5, 483–494 (2004).
Kalivas, P. W. The glutamate homeostasis hypothesis of addiction. Nat. Rev. Neurosci. 10, 561–572 (2009).
Everitt, B. J. & Robbins, T. W. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci. 8, 1481–1489 (2005).
Bossert, J. M., Marchant, N. J., Calu, D. J. & Shaham, Y. The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology 229, 453–457 (2013).
Piazza, P. V. & Deroche-Gamonet, V. A multistep general theory of transition to addiction. Psychopharmacology 229, 387–413 (2013).
Schuster, C. R. & Thompson, T. Self administration of and behavioral dependence on drugs. Annu. Rev. Pharmacol. 9, 483–502 (1969).
Brady, J. V. Animal models for assessing drugs of abuse. Neurosci. Biobehav. Rev. 15, 35–43 (1991).
Epstein, D. H., Preston, K. L., Stewart, J. & Shaham, Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology 189, 1–16 (2006).
Sinha, R., Shaham, Y. & Heilig, M. Translational and reverse translational research on the role of stress in drug craving and relapse. Psychopharmacology 218, 69–82 (2011).
Dole, V. P. & Nyswander, M. A. Medical treatment for diacetylmorphine (heroin) addiction. A clinical trial with methadone hydrochloride. JAMA 193, 646–650 (1965).
Jasinski, D. R., Pevnick, J. S. & Griffith, J. D. Human pharmacology and abuse potential of the analgesic buprenorphine: a potential agent for treating narcotic addiction. Arch. Gen. Psychiatry 35, 501–516 (1978).
Higgins, S. T. et al. A behavioral approach to achieving initial cocaine abstinence. Am. J. Psychiatry 148, 1218–1224 (1991).
Satel, S. & Lilienfeld, S. O. Addiction and the brain-disease fallacy. Front. Psychiatry 4, 141 (2013).
Kalant, H. What neurobiology cannot tell us about addiction. Addiction 105, 780–789 (2010).
Berkman, L. F. & Kawachi, I. Social Epidemiology (Oxford Univ. Press, 2000).
Havassy, B. E., Hall, S. M. & Wasserman, D. A. Social support and relapse: commonalities among alcoholics, opiate users, and cigarette smokers. Addict. Behav. 16, 235–246 (1991).
Mantsch, J. R., Baker, D. A., Funk, D., Le, A. D. & Shaham, Y. Stress-induced reinstatement of drug seeking: 20 years of progress. Neuropsychopharmacology 41, 335–356 (2016).
Marlatt, G. A., Baer, J. S., Donovan, D. M. & Kivlahan, D. R. Addictive behaviors: etiology and treatment. Annu. Rev. Psychol. 39, 223–252 (1988).
Brownell, K. D., Marlatt, G. A., Lichtenstein, E. & Wilson, G. T. Understanding and preventing relapse. Am. Psychol. 41, 765–782 (1986).
Eisenberger, N. I. The pain of social disconnection: examining the shared neural underpinnings of physical and social pain. Nat. Rev. Neurosci. 13, 421–434 (2012).
Wager, T. D. et al. An fMRI-based neurologic signature of physical pain. N. Engl. J. Med. 368, 1388–1397 (2013).
Garavan, H. Insula and drug cravings. Brain Struct. Funct. 214, 593–601 (2010).
Naqvi, N. H., Rudrauf, D., Damasio, H. & Bechara, A. Damage to the insula disrupts addiction to cigarette smoking. Science 315, 531–534 (2007).
Dinur-Klein, L. et al. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: a prospective, randomized controlled trial. Biol. Psychiatry 76, 742–749 (2014).
Sullivan, E. V. et al. A selective insular perfusion deficit contributes to compromised salience network connectivity in recovering alcoholic men. Biol. Psychiatry 74, 547–555 (2013).
Senatorov, V. V. et al. Reduced anterior insula, enlarged amygdala in alcoholism and associated depleted von Economo neurons. Brain 138, 69–79 (2015).
Butti, C., Santos, M., Uppal, N. & Hof, P. R. Von Economo neurons: clinical and evolutionary perspectives. Cortex 49, 312–326 (2013).
Naqvi, N. H., Gaznick, N., Tranel, D. & Bechara, A. The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Ann. NY Acad. Sci. 1316, 53–70 (2014).
Singer, T., Critchley, H. D. & Preuschoff, K. A common role of insula in feelings, empathy and uncertainty. Trends Cogn. Sci. 13, 334–340 (2009).
Gowin, J. L. et al. Attenuated insular processing during risk predicts relapse in early abstinent methamphetamine-dependent individuals. Neuropsychopharmacology 39, 1379–1387 (2014).
Uddin, L. Q. Salience processing and insular cortical function and dysfunction. Nat. Rev. Neurosci. 16, 55–61 (2015).
Morgan, D. et al. Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat. Neurosci. 5, 169–174 (2002).
Martinez, D. et al. Dopamine type 2/3 receptor availability in the striatum and social status in human volunteers. Biol. Psychiatry 67, 275–278 (2010).
Volkow, N. D., Fowler, J. S., Wang, G. J., Swanson, J. M. & Telang, F. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch. Neurol. 64, 1575–1579 (2007).
Chikama, M., McFarland, N. R., Amaral, D. G. & Haber, S. N. Insular cortical projections to functional regions of the striatum correlate with cortical cytoarchitectonic organization in the primate. J. Neurosci. 17, 9686–9705 (1997).
Leong, J. K., Pestilli, F., Wu, C. C., Samanez-Larkin, G. R. & Knutson, B. White-matter tract connecting anterior insula to nucleus accumbens correlates with reduced preference for positively skewed gambles. Neuron 89, 63–69 (2016).
Cho, Y. T., Ernst, M. & Fudge, J. L. Cortico–amygdala–striatal circuits are organized as hierarchical subsystems through the primate amygdala. J. Neurosci. 33, 14017–14030 (2013).
Nieuwenhuys, R. The insular cortex: a review. Prog. Brain Res. 195, 123–163 (2012).
Heilig, M. & Koob, G. F. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci. 30, 399–406 (2007).
Orban, C. et al. Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients. Am. J. Drug Alcohol Abuse 39, 433–440 (2013).
Machin, A. J. & Dunbar, R. I. M. The brain opioid theory of social attachment: a review of the evidence. Behaviour 148, 985–1025 (2011).
Panksepp, J., Herman, B. H., Vilberg, T., Bishop, P. & DeEskinazi, F. G. Endogenous opioids and social behavior. Neurosci. Biobehav. Rev. 4, 473–487 (1980).
Moles, A., Kieffer, B. L. & D'Amato, F. R. Deficit in attachment behavior in mice lacking the μ-opioid receptor gene. Science 304, 1983–1986 (2004).
Fabre-Nys, C., Meller, R. E. & Keverne, E. B. Opiate antagonists stimulate affiliative behaviour in monkeys. Pharmacol. Biochem. Behav. 16, 653–659 (1982).
Panksepp, J., Herman, B., Conner, R., Bishop, P. & Scott, J. P. The biology of social attachments: opiates alleviate separation distress. Biol. Psychiatry 13, 607–618 (1978).
Barr, C. S. et al. Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc. Natl Acad. Sci. USA 105, 5277–5281 (2008).
Copeland, W. E. et al. Child μ-opioid receptor gene variant influences parent-child relations. Neuropsychopharmacology 36, 1165–1170 (2011).
Baumgartner, U. et al. High opiate receptor binding potential in the human lateral pain system. Neuroimage 30, 692–699 (2006).
Way, B. M., Taylor, S. E. & Eisenberger, N. I. Variation in the μ-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. Proc. Natl Acad. Sci. USA 106, 15079–15084 (2009).
Hsu, D. T. et al. Response of the μ-opioid system to social rejection and acceptance. Mol. Psychiatry 18, 1211–1217 (2013).
Lutz, P. E. & Kieffer, B. L. The multiple facets of opioid receptor function: implications for addiction. Curr. Opin. Neurobiol. 23, 473–479 (2013).
Mick, I. et al. Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers. Neuropsychopharmacology 41, 1742–1750 (2016).
Khantzian, E. J. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv. Rev. Psychiatry 4, 231–244 (1997).
Mitchell, J. M. et al. Alcohol consumption induces endogenous opioid release in the human orbitofrontal cortex and nucleus accumbens. Sci. Transl Med. 4, 116ra6 (2012).
Lucantonio, F., Stalnaker, T. A., Shaham, Y., Niv, Y. & Schoenbaum, G. The impact of orbitofrontal dysfunction on cocaine addiction. Nat. Neurosci. 22, 358–366 (2012).
de Wit, H. Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict. Biol. 14, 22–31 (2009).
Bickel, W. K. & Marsch, L. A. Toward a behavioral economic understanding of drug dependence: delay discounting processes. Addiction 96, 73–86 (2001).
MacKillop, J. et al. Delayed reward discounting and addictive behavior: a meta-analysis. Psychopharmacology 216, 305–321 (2011).
Uekermann, J. & Daum, I. Social cognition in alcoholism: a link to prefrontal cortex dysfunction? Addiction 103, 726–735 (2008).
Preller, K. H. et al. Impaired emotional empathy and related social network deficits in cocaine users. Addict. Biol. 19, 452–466 (2014).
North, C. S., Eyrich, K. M., Pollio, D. E. & Spitznagel, E. L. Are rates of psychiatric disorders in the homeless population changing? Am. J. Publ. Health 94, 103–108 (2004).
Mullainathan, S. & Shafir, E. Scarcity: Why Having Too Little Means So Much (Times Books, 2013).
Wise, R. A. & Bozarth, M. A. A psychomotor stimulant theory of addiction. Psychol. Rev. 94, 469–492 (1987).
Anthony, J. C., Warner, L. A. & Kessler, R. C. Comparative epidemiology of dependence on tobacco, alcohol, controlled substances, and inhalants: basic findings from the National Comorbidity Survey. Exp. Clin. Psychopharmacol. 2, 244–268 (1994).
Kendler, K. S. et al. Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat. Neurosci. 15, 181–189 (2012).
Lopez-Quintero, C. et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 115, 120–130 (2011).
Wolffgramm, J. & Heyne, A. From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat. Behav. Brain Res. 70, 77–94 (1995).
Ahmed, S. H. Validation crisis in animal models of drug addiction: beyond non-disordered drug use toward drug addiction. Neurosci. Biobehav. Rev. 35, 172–184 (2010).
Nader, M. A. & Woolverton, W. L. Effects of increasing the magnitude of an alternative reinforcer on drug choice in a discrete-trials choice procedure. Psychopharmacology 105, 169–174 (1991).
Bozarth, M. A. & Wise, R. A. Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat. JAMA 254, 81–83 (1985).
Johanson, C. E., Balster, R. L. & Bonese, K. Self-administration of psychomotor stimulant drugs: the effects of unlimited access. Pharmacol. Biochem. Behav. 4, 45–51 (1976).
Cantin, L. et al. Cocaine is low on the value ladder of rats: possible evidence for resilience to addiction. PLoS ONE 5, e11592 (2010).
Caprioli, D. et al. Effect of the novel positive allosteric modulator of metabotropic glutamate receptor 2 AZD8529 on incubation of methamphetamine craving after prolonged voluntary abstinence in a rat model. Biol. Psychiatry 78, 463–473 (2015).
Deroche-Gamonet, V., Belin, D. & Piazza, P. V. Evidence for addiction-like behavior in the rat. Science 305, 1014–1017 (2004).
Krasnova, I. N. et al. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence. Neuropsychopharmacology 39, 2008–2016 (2014).
Nader, M. A. & Banks, M. L. Environmental modulation of drug taking: nonhuman primate models of cocaine abuse and PET neuroimaging. Neuropharmacology 76, 510–517 (2014).
Bardo, M. T., Neisewander, J. L. & Kelly, T. H. Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharmacol. Rev. 65, 255–290 (2013).
Miczek, K. A., Yap, J. J. & Covington, H. E. III. Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol. Ther. 120, 102–128 (2008).
Neisewander, J. L., Peartree, N. A. & Pentkowski, N. S. Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction. Psychopharmacology 224, 33–56 (2012).
Lu, L., Shepard, J. D., Hall, F. S. & Shaham, Y. Effect of environmental stressors on opiate and psychostimulant reinforcement, reinstatement and discrimination in rats: a review. Neurosci. Biobehav. Rev. 27, 457–491 (2003).
Bruchas, M. R., Land, B. B. & Chavkin, C. The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Res. 1314, 44–55 (2010).
Alexander, B. K., Coambs, R. B. & Hadaway, P. F. The effect of housing and gender on morphine self-administration in rats. Psychopharmacology 58, 175–179 (1978).
Meisch, R. A. & Carroll, M. E. in Methods of Assessing the Reinforcing Properties of Abused Drugs (ed. Bozarth, M. A.) 143–161 (Springer, 1987).
Bozarth, M. A., Murray, A. & Wise, R. A. Influence of housing conditions on the acquisition of intravenous heroin and cocaine self-administration in rats. Pharmacol. Biochem. Behav. 33, 903–907 (1989).
Wolffgramm, J. & Heyne, A. Social behavior, dominance, and social deprivation of rats determine drug choice. Pharmacol. Biochem. Behav. 38, 389–399 (1991).
Solinas, M., Thiriet, N., Chauvet, C. & Jaber, M. Prevention and treatment of drug addiction by environmental enrichment. Prog. Neurobiol. 92, 572–592 (2010).
Blanchard, D. C. & Blanchard, R. J. Behavioral correlates of chronic dominance–subordination relationships of male rats in a seminatural situation. Neurosci. Biobehav Rev. 14, 455–462 (1990).
Blanchard, R. J., Hori, K., Tom, P. & Blanchard, D. C. Social structure and ethanol consumption in the laboratory rat. Pharmacol. Biochem. Behav. 28, 437–442 (1987).
Heyne, A. The development of opiate addiction in the rat. Pharmacol. Biochem. Behav. 53, 11–25 (1996).
Helms, C. M., McClintick, M. N. & Grant, K. A. Social rank, chronic ethanol self-administration, and diurnal pituitary-adrenal activity in cynomolgus monkeys. Psychopharmacology 224, 133–143 (2012).
Jupp, B. et al. Social dominance in rats: effects on cocaine self-administration, novelty reactivity and dopamine receptor binding and content in the striatum. Psychopharmacology 233, 579–589 (2015).
Volkow, N. D., Fowler, J. S., Wang, G. J. & Swanson, J. M. Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol. Psychiatry 9, 557–569 (2004).
Nader, M. A. et al. Social dominance in female monkeys: dopamine receptor function and cocaine reinforcement. Biol. Psychiatry 72, 414–421 (2012).
Cahill, L. Sex influences on brain and emotional memory: the burden of proof has shifted. Prog. Brain Res. 186, 29–40 (2010).
Nader, M. A., Czoty, P. W., Gould, R. W. & Riddick, N. V. Review. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction. Phil. Trans. R. Soc. B 363, 3223–3232 (2008).
Eisenberger, N. I., Lieberman, M. D. & Williams, K. D. Does rejection hurt? An fMRI study of social exclusion. Science 302, 290–292 (2003).
Czoty, P. W. & Nader, M. A. Effects of oral and intravenous administration of buspirone on food–cocaine choice in socially housed male cynomolgus monkeys. Neuropsychopharmacology 40, 1072–1083 (2015).
Shaham, Y., Shalev, U., Lu, L., De Wit, H. & Stewart, J. The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168, 3–20 (2003).
Shaham, Y., Erb, S. & Stewart, J. Stress-induced relapse to heroin and cocaine seeking in rats: a review. Brain Res. Brain Res. Rev. 33, 13–33 (2000).
Jobes, M. L. et al. Clonidine blocks stress-induced craving in cocaine users. Psychopharmacology 218, 83–88 (2011).
Kowalczyk, W. J. et al. Clonidine maintenance prolongs opioid abstinence and decouples stress from craving in daily life: a randomized controlled trial with ecological momentary assessment. Am. J. Psychiatry 172, 760–767 (2015).
Vendruscolo, L. F. et al. Corticosteroid-dependent plasticity mediates compulsive alcohol drinking in rats. J. Neurosci. 32, 7563–7571 (2012).
Vendruscolo, L. F. et al. Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals. J. Clin. Invest. 125, 3193–3197 (2015).
Grimm, J. W., Hope, B. T., Wise, R. A. & Shaham, Y. Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412, 141–142 (2001).
Bedi, G. et al. Incubation of cue-induced cigarette craving during abstinence in human smokers. Biol. Psychiatry 69, 708–711 (2011).
Caprioli, D. et al. Ambience and drug choice: cocaine- and heroin-taking as a function of environmental context in humans and rats. Biol. Psychiatry 65, 893–899 (2009).
Xue, Y. X. et al. A memory retrieval–extinction procedure to prevent drug craving and relapse. Science 336, 241–245 (2012).
Cunningham, K. A., Bradberry, C. W., Chang, A. S. & Reith, M. E. The role of serotonin in the actions of psychostimulants: molecular and pharmacological analyses. Behav. Brain Res. 73, 93–102 (1996).
Schmitz, J. M. et al. Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug Alcohol Depend. 63, 207–214 (2001).
Robinson, T. E. & Berridge, K. C. The neural basis of drug craving: an incentive–sensitization theory of addiction. Brain Res. Rev. 18, 247–291 (1993).
Bradberry, C. W. Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys, and humans: areas of agreement, disagreement, and implications for addiction. Psychopharmacology 191, 705–717 (2007).
Anton, R. F. et al. A randomized, multicenter, double-blind, placebo-controlled study of the efficacy and safety of aripiprazole for the treatment of alcohol dependence. J. Clin. Psychopharmacol. 28, 5–12 (2008).
Tiihonen, J. et al. A comparison of aripiprazole, methylphenidate, and placebo for amphetamine dependence. Am. J. Psychiatry 164, 160–162 (2007).
Nutt, D. J., Lingford-Hughes, A., Erritzoe, D. & Stokes, P. R. The dopamine theory of addiction: 40 years of highs and lows. Nat. Rev. Neurosci. 16, 305–312 (2015).
Badiani, A., Belin, D., Epstein, D., Calu, D. & Shaham, Y. Opiate versus psychostimulant addiction: the differences do matter. Nat. Rev. Neurosci. 12, 685–700 (2011).
Thomas, M. J., Kalivas, P. W. & Shaham, Y. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction. Br. J. Pharmacol. 154, 327–342 (2008).
Wolf, M. E. & Ferrario, C. R. AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine. Neurosci. Biobehav. Rev. 35, 185–211 (2010).
LaRowe, S. D. et al. A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence. Am. J. Addict. 22, 443–452 (2013).
Le, A. D., Harding, S., Juzytsch, W., Fletcher, P. J. & Shaham, Y. The role of corticotropin-releasing factor in the median raphe nucleus in relapse to alcohol. J. Neurosci. 22, 7844–7849 (2002).
Kwako, L. E. et al. The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study. Neuropsychopharmacology 40, 1053–1063 (2015).
Schwandt, M. L. et al. The CRF1 antagonist verucerfont in anxious alcohol dependent women: translation of neuroendocrine, but not of anti-craving effects. Neuropsychopharmacology http://dx.doi.org/10.1038/npp.2016.61 (2016).
Coric, V. et al. Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder. Depress. Anxiety 27, 417–425 (2010).
Binneman, B. et al. A 6-week randomized, placebo-controlled trial of CP-316,311 (a selective CRH1 antagonist) in the treatment of major depression. Am. J. Psychiatry 165, 617–620 (2008).
Grillon, C. et al. The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle. Neuropsychopharmacology 40, 1064–1071 (2015).
Maurage, P. et al. Disrupted regulation of social exclusion in alcohol-dependence: an fMRI study. Neuropsychopharmacology 37, 2067–2075 (2012).
Acknowledgements
The writing of this article was supported in part by a grant from the Swedish Research Council (M.H.), the Intramural Research Program of the US National Institutes of Health and the US National Institute on Drug Abuse (D.H.E. and Y.S.) and grants DA010584 and DA017763 (M.A.N.). The authors are grateful to S. N. Haber at the University of Rochester, New York, USA, and her co-workers for producing and providing Figure 3. The authors apologize to their many friends and colleagues for not citing many reviews and empirical papers relevant to the topic of their paper, owing to format restrictions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Glossary
- Compulsive drug use
-
Continued use of a drug despite (known) adverse consequences.
- Contingency management
-
A treatment based on systematic reinforcement of a desired, clinically beneficial behaviour.
- Craving
-
The subjective experience of a strong desire to consume a particular substance, to experience its effects or to avoid the symptoms of its withdrawal.
- Drug addiction
-
A clinical condition in which an individual knowingly continues to pursue and consume a chemical substance in a manner that is harmful to that individual or to others.
- Pain matrix
-
A term proposed for a set of brain structures, including the anterior insula and the dorsal anterior cingulate cortex, that are consistently shown by functional MRI to be activated during physical pain.
- Postdictive validity
-
The ability to retrospectively demonstrate an established human phenomenon in an animal model.
- Predictive validity
-
In the context of medications development, the extent to which a drug effect in laboratory animals prospectively predicts therapeutic effects of the same drug in humans.
- Protracted withdrawal
-
The affective symptoms of drug withdrawal — including low mood, elevated anxiety and increased sensitivity to stress — that persist beyond the time frame of acute physical withdrawal (which typically does not last beyond 3–7 days).
- Reinstatement
-
In the context of addiction research, the resumption of drug seeking after extinction of the drug-reinforced responding, induced by exposure to priming doses of drug, drug cues or stressors.
- Relapse
-
Resumption of drug taking after achieving abstinence.
- Social defeat
-
A type of social stress used in laboratory-animal studies that is typically induced by placing a rodent in a cage with an unfamiliar rodent that is expected to attack and defeat the intruder, owing to increased strength, aggression or established dominance.
- Social integration
-
A central concept of sociology, developed by the French sociologist Émile Durkheim, that refers to the web of relationships and interactions — family, kinship groups, traditions or economic activity — through which individuals are connected to each other to form a society; social exclusion is defined as a failure of this process.
Rights and permissions
About this article
Cite this article
Heilig, M., Epstein, D., Nader, M. et al. Time to connect: bringing social context into addiction neuroscience. Nat Rev Neurosci 17, 592–599 (2016). https://doi.org/10.1038/nrn.2016.67
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrn.2016.67
This article is cited by
-
An automated group-housed oral fentanyl self-administration method in mice
Psychopharmacology (2024)
-
An economon model of drug addiction
Psychopharmacology (2024)
-
An operant social self-administration and choice model in mice
Nature Protocols (2023)
-
Male-selective effects of oxytocin agonism on alcohol intake: behavioral assessment in socially housed prairie voles and involvement of RAGE
Neuropsychopharmacology (2023)
-
Rats choose alcohol over social reward in an operant choice procedure
Neuropsychopharmacology (2023)