Extinction of Heroin Seeking Does Not Require the Infralimbic Cortex or Its Projections to the Nucleus Accumbens Shell or Amygdala

Matthew S McGregor; Kelle E Nett; Subhash C Gupta; John A Wemmie; Ryan T LaLumiere

doi:10.1111/adb.70092

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Extinction of Heroin Seeking Does Not Require the Infralimbic Cortex or Its Projections to the Nucleus Accumbens Shell or Amygdala

Journal article

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Extinction of Heroin Seeking Does Not Require the Infralimbic Cortex or Its Projections to the Nucleus Accumbens Shell or Amygdala

Matthew S McGregor, Kelle E Nett, Subhash C Gupta, John A Wemmie and Ryan T LaLumiere

Addiction biology, Vol.30(10), e70092

10/2025

DOI: 10.1111/adb.70092

PMCID: PMC12538630

PMID: 41117403

Appears in UI Libraries Support Open Access

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Abstract

Evidence indicates that the activity of the infralimbic cortex (IL), as well as its projections to the nucleus accumbens shell (NAshell) and amygdala, following an unreinforced lever press is critical for cocaine extinction learning and retention. It is unclear whether the same neural circuitry is involved in extinction encoding for other classes of addictive drugs, including opioids. In this study, we used a behaviour-controlled optogenetic approach in female and male Sprague-Dawley rats to examine the role of the IL and its projections in the extinction of heroin seeking. Rats first underwent 12+ days of 6- or 3-h heroin self-administration sessions, followed by 12 days of extinction training. Optogenetic inhibition of the IL, IL-NAshell or IL-amygdala pathway was given for 20 s immediately following an unreinforced lever press during the first 5 days of extinction. Unlike cocaine extinction, these manipulations had no effect on lever pressing during extinction training, nor on the retention of extinction learning, as assessed during the subsequent 7 days of extinction without optogenetic inhibition. These results suggest that the extinction of heroin seeking does not involve the same infralimbic mechanisms that are critical for the extinction of cocaine seeking. Although extinction learning did not differ by sex, analyses of self-administration data revealed that females self-administered more heroin than males in 3 h, but not 6 h, self-administration sessions, indicating session length-dependent sex differences in heroin taking.

Amygdala - drug effects

Amygdala - physiology

Animals

Conditioning, Operant

Drug-Seeking Behavior - drug effects

Drug-Seeking Behavior - physiology

Extinction, Psychological - drug effects

Extinction, Psychological - physiology

Female

Heroin - administration & dosage

Heroin - pharmacology

Heroin Dependence - physiopathology

Male

Narcotics - administration & dosage

Narcotics - pharmacology

Neural Pathways

Nucleus Accumbens - drug effects

Nucleus Accumbens - physiology

Optogenetics

Rats

Rats, Sprague-Dawley

Self Administration

UIOWA OA Agreement

Details

Title: Subtitle: Extinction of Heroin Seeking Does Not Require the Infralimbic Cortex or Its Projections to the Nucleus Accumbens Shell or Amygdala
Creators: Matthew S McGregor - University of Iowa
Kelle E Nett - University of Iowa
Subhash C Gupta - University of Iowa
John A Wemmie - University of Iowa
Ryan T LaLumiere - University of Iowa
Resource Type: Journal article
Publication Details: Addiction biology, Vol.30(10), e70092
DOI: 10.1111/adb.70092
PMID: 41117403
PMCID: PMC12538630
NLM abbreviation: Addict Biol
ISSN: 1355-6215
eISSN: 1369-1600
Publisher: Wiley
Grant note: 5R01DA037216 / NIDA NIH HHS 5R01DA048055 / NIDA NIH HHS IO1BX004440 / Dept. of Veterans Affairs R01DA052953 / NIDA NIH HHS Roy J. Carver Charitable Trust
Language: English
Date published: 10/2025
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9985019040102771

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