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Updated: Nov 15, 2025

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A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
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Trial-based Discrimination Procedure for Studying Drug Relapse in Rats
Veronica A Lennon1, Megan B Brenner1, Sophia J Weber1
1Neuronal Ensembles in Addiction Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States.
Bio-Protocol
|March 3, 2021
Summary
Drug cues that signal reward availability, known as discriminative stimuli (DSs), can drive relapse in abstinent individuals. Our research shows that cocaine seeking behavior controlled by DSs also incubates over time in rats, persisting for months.
Area of Science:
- Neuroscience
- Behavioral Science
- Addiction Research
Background:
- Drug addiction relapse is a major clinical challenge.
- Cues associated with drug use can trigger relapse in abstinent individuals.
- Existing animal models often focus on conditioned stimuli (CSs) rather than discriminative stimuli (DSs).
Purpose of the Study:
- To detail a behavioral protocol for studying discriminative stimuli (DSs) in the context of drug relapse.
- To investigate the incubation of drug craving and seeking behavior mediated by DSs.
- To provide a foundation for future neurobiological investigations into DS-mediated relapse.
Main Methods:
- Rats were trained to discriminate between two light cues: one signaling cocaine availability (DS+) and another signaling its absence (DS-).
- A trial-based procedure was employed, requiring lever pressing during DS+ and suppression during DS-.
- The protocol facilitates time-locked in vivo recordings and manipulations.
Main Results:
- Rats successfully learned to discriminate between the DS+ and DS- cues.
- Cocaine seeking behavior controlled by DSs was shown to incubate during abstinence.
- This DS-controlled seeking persisted for up to 300 days of abstinence.
Conclusions:
- Discriminative stimuli (DSs) play a significant role in drug relapse.
- The incubation of DS-controlled drug seeking is a robust phenomenon in animal models.
- This protocol enables detailed neurobiological studies of DS contributions to addiction and relapse prevention strategies.

