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Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration
Journal article   Open access   Peer reviewed

Dissociating the incubation of appetitive and consummatory behavior in a model of oral cocaine self-administration

Mark Douglas Namba, Samuel L. Goldberg, Christine Marie Side, Abhiram Yadlapalli, Christina M Curran-Alfaro, Devin Kress, Melissa F. Fogarty, Amanda L.A. Mohr and Jacqueline M Barker
Pharmacology, biochemistry and behavior, v 254, 174055
Sep 2025
PMID: 40582418
Featured in Collection :   Research Supported by Drexel Libraries' OA Programs
url
https://doi.org/10.1016/j.pbb.2025.174055View
Published, Version of Record (VoR)Open Access via Drexel Libraries Read and Publish Program 2025CC BY-NC-ND V4.0 Restricted

Abstract

Cocaine relapse Cocaine craving Nucleus accumbens GLT-1 Glutamate Cocaine
Cocaine use disorder remains a persistent public health dilemma that currently lacks effective treatment strategies. One key impediment to successful treatment outcomes is increased drug craving that occurs over the course of abstinence and subsequent relapse to drug use. This phenomenon, known as the incubation of drug craving, has been modeled extensively in rodent models of intravenous drug self-administration. The design of most intravenous self-administration studies examining the incubation effect precludes disentangling appetitive and consummatory behaviors as drug seeking (appetitive) and taking (consummatory) is simultaneous. Here, we employed a model of oral cocaine self-administration to interrogate the incubation of drug vs nondrug craving, where the route of administration is identical between reinforcers and appetitive and consummatory behaviors are dissociable. Oral self-administration of cocaine produced detectable levels of cocaine and its metabolite, benzoylecgonine, within the blood and brain, and tissue levels of both substrates correlated with cocaine consumption. When tested for seeking- (lever pressing) and taking-related (magazine head entries) behavior after 1 or 21 days of forced abstinence, we observed incubation of lever pressing among cocaine-administering mice and incubation of magazine entries among saccharin-administering mice. These behavioral changes were accompanied by reduced expression of the glial glutamate transporter GLT-1 within the nucleus accumbens (NAc) of cocaine self-administering mice, regardless of abstinence. Altogether, these results underscore the utility of this model of cocaine self-administration, highlight the conserved nature of incubated cocaine seeking across routes of administration, and demonstrate the dissociable neurobehavioral sequelae of the incubation of reward seeking across reinforcer types.

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Web of Science research areas
Behavioral Sciences
Neurosciences
Pharmacology & Pharmacy
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