Pathways to the persistence of drug use despite its adverse consequences.

The persistence of drug taking despite its adverse consequences plays a central role in the presentation, diagnosis, and impacts of addiction. Eventual recognition and appraisal of these adverse consequences is central to decisions to reduce or cease use. However, the most appropriate ways of conceptualizing persistence in the face of adverse consequences remain unclear. Here we review evidence that there are at least three pathways to persistent use despite the negative consequences of that use. A cognitive pathway for recognition of adverse consequences, a motivational pathway for valuation of these consequences, and a behavioral pathway for responding to these adverse consequences. These pathways are dynamic, not linear, with multiple possible trajectories between them, and each is sufficient to produce persistence. We describe these pathways, their characteristics, brain cellular and circuit substrates, and we highlight their relevance to different pathways to self- and treatment-guided behavior change.