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Updated: Jun 22, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
A stimulus-control account of dysregulated drug intake
Leigh V Panlilio1, Eric B Thorndike, Charles W Schindler
1Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, 251 Bayview Blvd, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov
Abstract:
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.
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