The Development and Maintenance of Drug Addiction - BLOG NOW

The development and maintenance of drug addiction (Link to full-length article)

Author(s): Roy A Wise and George F Koob


What is the defining property of addiction? We dust off a several-decades-long debate about the relative importance of two forms of reinforcement—positive reinforcement, subjectively linked to drug-induced euphoria, and negative reinforcement, subjectively linked to the alleviation of pain—both of which figure importantly in addiction theory; each of these forms has dominated addiction theory in its time. We agree that addiction begins with the formation of habits through positive reinforcement and that drug-opposite physiological responses often establish the conditions for negative reinforcement to come into play at a time when tolerance, in the form of increasing reward thresholds, appears to develop into positive reinforcement. Wise’s work has tended to focus on positive-reinforcement mechanisms that are important for establishing drug-seeking habits and reinstating them quickly after periods of abstinence, whereas Koob’s work has tended to focus on the negative-reinforcement mechanisms that become most obvious in the late stages of sustained addiction. While we tend to agree with each other about the early and late stages of addiction, we hold different views as to (i) the point between early and late at which the diagnosis of ‘addiction’ should be invoked, (ii) the relative importance of positive and negative reinforcement leading up to this transition, and (iii) the degree to which the specifics of negative reinforcement can be generalized across the range of addictive agents.


Our inaugural Circumspectives is entitled “The development and maintenance of drug addiction”, authored by Roy A. Wise and George F. Koob (2014).  The authors are eminent addiction researchers who have had a tremendous influence on the field, through both their research and generative spirits.  For decades they have had a rather famous scientific disagreement, centered on their opposing views about what motivates addictive behavior.  Dr. Wise is a proponent of the idea that the positive (rewarding) effects of abused drugs are most important, whereas Dr. Koob’s theory is that it is the aversive effects of drug withdrawal (the “Dark Side”) that are critical.
We welcome your thoughts on this debate and, if you wish to share them, your own ideas for experiments that would help to resolve this debate and push the field forward.
Bill Carlezon, Ph.D., on behalf of the Editors of NPP.
Dr Koob states "the allostasis-like changes in the reward system that I consider compulsive-like are generally evident only in animal models with the extended-access paradigms associated with escalation in drug intake". The LgA model has gained dominance in the field as one of the best animal models of addiction. Granted, we cannot make rats stand in bus shelters smoking crack. But this should not deter us from asking how well the LgA model reflects reality. With this model, animals are exposed daily to continuously high brain levels of drug for weeks, sometimes months on end. As Dr Koob argues, 'allostasis-like changes in the reward system' preferentially occur in these rats. But is this how addicts take drugs? For several reasons easy to imagine, it is rather unlikely that addicts maintain high brain levels of drug on a nearly continuous basis. Some clinical researchers who have taken the time to study the temporal patterns of drug use, in particular for cocaine, find that cocaine addicts use intermittently—and do so willingly. As argued and illustrated by Dave Roberts' group, it might be time to pay attention to this, and revisit the LgA model to see if it truly captures how addicts expose their brains to drug. Because if this is not how addicts do it, then it is not how our rats should do it either.
Anne-Noël Samaha
Posted: Aug 29, 2014 9:03 AM
Perhaps the antagonists are describing two sides of the one coin. Is the alleviation of withdrawal rewarding? Does the "dark side" make reward de-escalate more rapidly? We see people totally detoxed but then relapse upon return to their usual haunts at the first cue. Is this driven by Koob's prolonged motivational withdrawal or is it an example of Wise's reinforced compulsive use. Or both.
Simon Holliday
Posted: Aug 03, 2014 7:57 AM
Thank you for taking the time to write. We are happy to take suggestions for future articles. I personally encourage ACNP members to take a more active role in their journal by taking the time to share their ideas of what types of articles they would like to see. Hopefully this is the first of many Circumspectives pieces that stimulate collegial discussion on matters of great importance to the college.
Bill Carlezon
Posted: Jan 25, 2014 9:51 AM

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