Evidence map›Paper›PMID 41652218›Full record

ArticlePsychopharmacology2026

C57 and DBA mouse strains express distinct cocaine avoidance phenotypes in an operant runway independent of differences in striatal dynorphin-enkephalin balance.

Bailey C Remmers, In Bae Choi, Kanako Matsumura, Amelia Nicot, Sydney Cox, Lauren K Dobbs

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Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Bailey C RemmersInterdisciplinary Neuroscience Program, The University of Texas at Austin, Austin, TX, USA.
In Bae ChoiDepartment of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Kanako MatsumuraInterdisciplinary Neuroscience Program, The University of Texas at Austin, Austin, TX, USA.
Amelia NicotDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA.
Sydney CoxDepartment of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Lauren K DobbsDepartment of Neuroscience, The University of Texas at Austin, Austin, TX, USA. ldobbs@austin.utexas.edu.ORCID http://orcid.org/0000-0001-7489-9977

Funding

Regulation of striatal microcircuits by endogenous opioids as a novel mechanism underlying cocaine seekingR01DA054329 · NIDA · UNIVERSITY OF TEXAS AT AUSTIN · PI Lauren K Dobbs · 2022 to 2026
$2.4M
Recruitment of striatal enkephalin by cocaine as a substrate for striatopallidal circuit adaptations and cocaine seekingF31DA058522 · NIDA · UNIVERSITY OF TEXAS AT AUSTIN · PI Kanako Matsumura · 2024 to 2026
$139k
Dell Medical School, University of Texas at Austin start-upNational Institute of Drug Abuse R01DA054329NIDA NIH HHS F31 DA058522NIDA NIH HHS R01 DA054329The University of Texas at Austin Rising STARsWaggoner Center for Alcohol and Addiction Research, University of Texas at Austin Bruce-Jones Fellowship
6 · The paper itself

Abstract

rationaleHuman self-report data and rodent models indicate cocaine can induce negative affect, which may impact future cocaine use severity. Despite this, understanding of the neurobiology driving cocaine avoidance is limited. Within the striatum, the opioid peptides enkephalin and dynorphin are associated with cocaine reward and aversion, respectively. Additionally, striatal dynorphin signaling resulting from stress or cocaine withdrawal acts as a negative reinforcer to increase cocaine seeking.

objectivesWe validated the use of the cocaine self-administration runway in mice to measure the development of cocaine avoidance and tested whether mice with higher relative striatal dynorphin-to-enkephalin expression are resistant to developing cocaine avoidance.

methodsCocaine avoidance in the self-administration runway was measured compared to positive (food) and neutral (saline) controls. We tested two inbred mouse strains, C57BL/6J and DBA/2J, known to have opposite striatal dynorphin/enkephalin milieus, and in mice lacking enkephalin selectively from striatal medium spiny neurons (D2-PenkKO).

resultsBoth inbred strains developed cocaine avoidance, though they expressed it differently. Across training, DBA/2J mice increased their latency to self-administer cocaine, and C57BL/6J increased the number of retreats away from the cocaine-paired goal box. D2-PenkKOs developed similar cocaine avoidance compared to littermate controls.

conclusionsMice develop avoidance to self-administer cocaine in the runway across a range of strains. Pre-existing strain differences in the striatal dynorphin/enkephalin milieu, however, do not appear to alter the development of cocaine avoidance, and striatal enkephalin is not necessary for the development of cocaine avoidance. This suggests higher relative striatal dynorphin does not facilitate cocaine seeking by mitigating cocaine avoidance.

Indexed as

Approach-avoidanceCocaine avoidanceCocaine self-administrationDynorphinEnkephalinInbred mouse strainsRunwayStriatum

Identifiers

PMID41652218

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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.