Pathways to the persistence of drug use despite its adverse consequences

Abstract

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.

Fig. 1. Pathways to insensitivity and their potential resolution.

At least three pathways, representing distinct psychological factors, may each be sufficient to produce insensitivity to punishment and cause persistent, detrimental behavior. Insensitivity can arise from poor instrumental contingency knowledge (cognitive pathway), distortions in positive and/or negative valuation of consequences (motivational pathway), and/or alterations in behavioral autonomy (behavioral pathway). These pathways occur against complex backgrounds of intoxication, history of dependence, acute or protracted withdrawal, and acute as well as chronic stressors that can influence capacity to detect, appropriately learn about, weight, and respond to negative consequences. These pathways can operate independently but may also interact. They are underpinned by still poorly understood distinct (as shown in colored) but partially overlapping (as shown in gray) neural circuitries. These pathways are likely dynamic and non-linear. Each may operate within the same individual at different times. Resolution of problematic behaviors will depend on which of these factors is contributing at specific times to cause persistence of behavior. dlPFC—dorsolateral prefrontal cortex, mPFC—medial prefrontal cortex, IC—insular cortex, Thal—thalamus, Str—striatum, DM—dorsomedial striatum, DL—dorsolateral striatum, V—ventral striatum, Ce—central amygdala, BL—basolateral amygdala complex.