Evidence map›Paper›PMID 41507314›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2026

Inactivation of NMDAR and CaMKII signaling within the prelimbic cortex blocks incubated cocaine- and sucrose-craving.

Laura L Huerta Sanchez, Natasha M Siao, Sanil R Chaudhari, Julie E Barrios, Audrey Y Na, Mirette G Tadros, Megan L McConnell, Rachel M Kaplan, Caden R Lane, Hoa H T Doan and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Laura L Huerta SanchezDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.ORCID http://orcid.org/0009-0001-0870-8252
Natasha M SiaoDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Sanil R ChaudhariDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Julie E BarriosDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Audrey Y NaDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Mirette G TadrosDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Megan L McConnellDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Rachel M KaplanDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Caden R LaneDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Hoa H T DoanDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Ashley B LigerDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Tessa C ChouDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Serena MarconDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Fernando J CanoDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Tod E KippinDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
Karen K SzumlinskiDepartment of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA. szumlinski@ucsb.edu.ORCID http://orcid.org/0000-0003-1078-1077

Funding

Incubated drug-craving and neurochemical interactionsR01DA053328 · NIDA · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI SZUMLINSKI, KAREN KATHLEEN · 2021 to 2025
$1.8M
Role of PL CaMKII in incubated cocaine-cravingF99NS141388 · NINDS · UNIVERSITY OF CALIFORNIA SANTA BARBARA · PI HUERTA SANCHEZ, LAURA · 2024 to 2024
$43k
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) Predoctoral ScholarshipNIDA NIH HHS R01 DA053328NINDS NIH HHS F99 NS141388U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS141388U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA053328U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA51100
6 · The paper itself

Abstract

The incubation of craving is a term coined to characterize the behavioral phenomenon wherein cue-elicited craving strengthens over a period of abstinence. Incubated cocaine-craving is mediated, at least in part, by increased glutamate release within the prelimbic cortex (PL). We hypothesized that this glutamate release stimulates NMDA-type glutamate receptors (NMDARs), leading to calcium-dependent activation of CaMKII signaling that drives incubated craving. To test this hypothesis, adult male and female Sprague-Dawley rats were trained to self-administer either intravenous cocaine or sucrose pellets (6 h/day × 10 days) and tested for cue-elicited cocaine- or sucrose-craving in early versus later (i.e., after incubation) withdrawal. Incubated cocaine-seeking was associated with increased CaMKII activity in the PL, but no change in NMDAR subunits. In contrast, incubated sucrose-craving was associated with many sex-dependent changes in both NMDAR subunit expression and CaMKII activation that were subregion-selective. An intra-PL infusion of the NMDA antagonist D-AP5 (2.5 or 7.5 µg/side) or the CaMKII inhibitor myr-AIP (10 pg/side) blocked both incubated cocaine- and sucrose-craving, with no effects detected in early withdrawal. Co-infusion of both D-AP5 and myr-AIP exerted a larger effect on incubated cocaine-craving than either antagonist alone. These data corroborate earlier evidence for distinct biochemical correlates within mPFC between incubated cocaine- and sucrose-craving and, for the first time, demonstrate that both NMDAR and CaMKII activation within the PL are common drivers of incubated craving of potential relevance to the design of anti-craving medications in the contexts of both drug and food reinforcers.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase Type 2CocaineCravingPrefrontal CortexReceptors, N-Methyl-D-AspartateSignal TransductionSucroseAnimalsExcitatory Amino Acid AntagonistsFemaleMaleRatsRats, Sprague-DawleySelf AdministrationCalcium-Calmodulin-Dependent Protein Kinase Type 2CocaineExcitatory Amino Acid AntagonistsReceptors, N-Methyl-D-AspartateSucrose

Identifiers

PMID41507314
PMCPMC13213044

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.