A stimulus-control account of dysregulated drug intake.

Drug self-administration typically occurs in a regular temporal pattern, with a consistent pause following each injection. We have proposed that this patterning results from differential reinforcement of post-injection pausing. In this view, even when every response produces an injection, some injections are not reinforcing because they occur when the level of drug effect is already maximal; consequently, drug reinforcement occurs on an intermittent schedule, and the interoceptive drug effect functions as a cue, indicating when another injection will be reinforcing. Previously, we emulated this situation with rats by using food reinforcement; each response was recorded as delivering a "virtual" injection, and a visual cue tracked the virtual drug level to indicate availability of reinforcement. This emulation schedule produced response patterns strikingly similar to actual drug self-administration. In the present study, the emulation schedule was modified to determine whether reinforcement of pausing is sufficient to produce these patterns, or whether a cue is necessary. Without a cue, response patterns were irregular and virtual drug intake was escalated. These results suggest that a failure of interoceptive cues to control pausing might contribute to the dysregulated drug intake that is associated with addiction.