Fig. 1. The four stages of memory-guided drug choice.

a During early use, various memoranda (“cues”—such as people, places, things, or even internal signals) are bound to the memory of positive drug experiences and also to drug-related “fantasies”—episodes which did not occur, but which are imagined on the basis of the material provided by drug experiences and associated rewards. b Over persistent use, these associations between cues, experience memories, and fantasies are strengthened, leading to rapid, involuntary reinstatement of the latter when presented with the former. These signals carry positive reward, thereby encouraging consumption and explaining persistent use despite lessening actual rewards and/or increasing negative consequences. c During treatment or other forms of abstinence, drug memories and fantasies persist and can be recalled, but now have competition in their effect on action selection, in the form of “drug-inconsistent” mental context: memories and imagined scenarios of alternative goods, e.g., of relationships, employment, health. Persistent abstinence suggests these memories have become bound to widely available cues, or are otherwise easily recalled. d However, the original, drug-consistent, memories are still available to recall. If a momentary influence—such as a shift in the environment, or an acute stressor—disrupts recall of drug-inconsistent associations, their effect on behavior can reduce, allowing drug-related memories to prevail.