Thalamo-accumbal circuit adaptations following extended oxycodone abstinence.
Overview
- Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, United States
- Department of Neuroscience & Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, United States
- Department of Neuroscience, University of Kentucky, Lexington, United States
- Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, United States
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, United States
Abstract
Opioid use disorder is characterized by compulsive drug seeking and heightened relapse vulnerability following abstinence, a phenomenon known as incubation of craving. Although preclinical data suggest similar behavioral expression of opioid use between sexes, conclusive evidence on sex differences in craving and relapse across abstinence periods remains lacking. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength, glutamate release probability, and intrinsic excitability of NAcSh medium spiny neurons (MSNs) following 1 (acute) or 14 (prolonged) days of forced abstinence. No sex differences were observed in oxycodone self-administration or somatic withdrawal. However, females exhibited greater cue-induced relapse after prolonged but not acute abstinence. Prolonged abstinence produced comparable increases in PVT-NAcSh synaptic strength and presynaptic glutamate release probability in both sexes, while inhibitory transmission and MSN excitability were largely unaltered. The dissociation between comparable circuit-level plasticity and sex-specific relapse vulnerability suggests that PVT-NAcSh strengthening represents a shared neuroadaptation to oxycodone abstinence, while mechanisms driving heightened relapse in females likely involve additional circuit elements that remain to be identified.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- doi:10.5061/
dryad.wwpzgmt13 , at Dryad; found in “Data availability”
Data availability
All data supporting the findings of this study have been deposited in the Dryad Digital Repository (doi: https://
The following dataset was generated:
Yanaira AC, Yan L, Nicholas C, Megan N, Gillian D, Yunona M, Grace C, Maria M, Vadim B, Elena C. 2026. Thalamo-accumbal circuit adaptations following extended oxycodone abstinence. Dryad Digital Repository.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 10 authors, 1 keyword, 12 MeSH terms, 2 funders, 61 references.
Cite
This paper
Alonso Caraballo, Y., Li, Y., Constantino, N. J., Neal, M. A., Driscoll, G. S., Manasian, Y., Cai, G. K., Mavrikaki, M., Bolshakov, V. Y., & Chartoff, E. (2026). Thalamo-accumbal circuit adaptations following extended oxycodone abstinence. eLife, 14, RP102189. https://
BibTeX
@article{alonsocaraballo
author = {Alonso Caraballo, Yanaira and Li, Yan and Constantino, Nicholas J and Neal, Megan A and Driscoll, Gillian S and Manasian, Yunona and Cai, Grace K and Mavrikaki, Maria and Bolshakov, Vadim Y and Chartoff, Elena},
title = {{Thalamo-accumbal circuit adaptations following extended oxycodone abstinence}},
journal = {eLife},
year = {2026},
month = aug,
volume = {14},
pages = {RP102189},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/
url = {https://
pmid = {42550587},
pmcid = {PMC13436959}
}
RIS
TY - JOUR
AU - Alonso Caraballo, Yanaira
AU - Li, Yan
AU - Constantino, Nicholas J
AU - Neal, Megan A
AU - Driscoll, Gillian S
AU - Manasian, Yunona
AU - Cai, Grace K
AU - Mavrikaki, Maria
AU - Bolshakov, Vadim Y
AU - Chartoff, Elena
TI - Thalamo-accumbal circuit adaptations following extended oxycodone abstinence
T2 - eLife
J2 - eLife
PY - 2026
DA - 2026/
VL - 14
SP - RP102189
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.7554/
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"container-title": "eLife",
"author": [
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"family": "Alonso Caraballo",
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"language": "en",
"issued": {
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