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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. Access through your institution Buy or

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ADDICTION AS A BRAIN DISEASE REVISED: WHY IT STILL MATTERS, AND THE NEED FOR CONSILIENCE Article Open access 22 February 2021 THE NEUROBIOLOGY OF DRUG ADDICTION: CROSS-SPECIES INSIGHTS INTO

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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 * Department of Clinical and Experimental Medicine (IKE), Center for Social and Affective Neuroscience, Linköping University, Linköping, SE-581 83,

Sweden Markus Heilig * Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, 21044, Maryland, USA David H. Epstein & Yavin Shaham *

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, 27157, North Carolina, USA Michael A. Nader Authors * Markus Heilig View author publications You can

also search for this author inPubMed Google Scholar * David H. Epstein View author publications You can also search for this author inPubMed Google Scholar * Michael A. Nader View author

publications You can also search for this author inPubMed Google Scholar * Yavin Shaham View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to Markus Heilig. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT

SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 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 Reprints 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 Download citation * Published: 09 June 2016 * Issue Date:

September 2016 * DOI: https://doi.org/10.1038/nrn.2016.67 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable

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