Brain Metabolic Correlates of Heroin Addiction Severity during Abstinence and Heroin versus Social Seeking: A PET Study in Rats.

Hot Off the Press – October 14, 2026

Published in Proceedings of the National Academy of Sciences by Ginevra D’Ottavio, Alana Sullivan et al. of the NIDA IRP Neurobiology of Relapse Section.

Summary

Researchers used a rat model to examine whether differences in heroin addiction-like behavior are linked to distinct patterns of brain metabolism during abstinence. Rats could self-administer heroin and were also given opportunities to choose between heroin and social interaction. The researchers combined measures of heroin intake, binge-like use, and preference for heroin over social interaction into a measure of addiction severity.

Brain imaging during 3 to 5 weeks of abstinence showed widespread metabolic differences between rats that had self-administered heroin and control rats. More importantly, individual differences in addiction severity were associated with activity in specific brain regions. At rest, greater addiction severity was linked to lower metabolism in the piriform cortex and higher metabolism in the ventral hippocampus. During heroin seeking, greater severity was associated with lower metabolism in the postsubiculum and cerebellum. These findings suggest that vulnerability to addiction may be reflected especially strongly in brain activity when animals are at rest, rather than only when they encounter drug-related cues.

Heroin exposure and addiction severity did not reduce the rats’ motivation for social interaction, and addiction severity was not associated with meaningful metabolic differences during social seeking. The findings identify brain metabolic patterns that could help researchers investigate vulnerability to opioid addiction, but the study was conducted in rats and did not establish whether these patterns can identify addiction risk or guide treatment in people.

Publication Information

D'Ottavio, Ginevra; Sullivan, Alana; Pilz, Emma; Schoenborn, Ingrid; Solis, Oscar; Gomez, Juan L; Kahnt, Thorsten; Michaelides, Michael; Shaham, Yavin

Brain metabolic correlates of heroin addiction severity during abstinence and heroin versus social seeking: A PET study in rats Journal Article

In: Proc Natl Acad Sci U S A, vol. 123, no. 36, pp. e2610087123, 2026, ISSN: 1091-6490.

Abstract | Links

@article{pmid42696536,

title = {Brain metabolic correlates of heroin addiction severity during abstinence and heroin versus social seeking: A PET study in rats},

author = {Ginevra D'Ottavio and Alana Sullivan and Emma Pilz and Ingrid Schoenborn and Oscar Solis and Juan L Gomez and Thorsten Kahnt and Michael Michaelides and Yavin Shaham},

url = {https://pubmed.ncbi.nlm.nih.gov/42696536/},

doi = {10.1073/pnas.2610087123},

issn = {1091-6490},

year  = {2026},

date = {2026-09-01},

urldate = {2026-09-01},

journal = {Proc Natl Acad Sci U S A},

volume = {123},

number = {36},

pages = {e2610087123},

abstract = {Only a subset of heroin users develop addiction, characterized by binge-like heroin use and preference for heroin over other rewards, including social rewards. We recently established a rat model that captures these features. We trained rats to lever-press for social interaction and heroin (or saline, control) infusions and then tested heroin and social seeking and heroin-vs.-social choice. During 3 to 5 abstinence weeks, we used 2-deoxy-2-[F]fluoro-D-glucose (FDG) positron emission tomography (PET) imaging to assess regional brain metabolic activity at rest (homecage) and during heroin and social seeking. We assessed regional differences in FDG uptake using unbiased voxel-wise analysis and statistical parametric mapping, and correlated FDG uptake with principle-component-analysis-derived addiction severity score incorporating heroin intake, binge-like episodes, and heroin preference. Compared with saline-trained rats, heroin-trained rats showed overall higher FDG uptake across multiple brain regions at rest and during both reward-seeking tests. Comparison of heroin-vs.-social-seeking in heroin-trained rats showed higher uptake in claustrum/striatum and auditory cortex during social seeking. Analysis of individual differences showed that addiction severity was primarily associated with metabolic alterations under resting conditions rather than during heroin or social seeking. At rest, higher addiction severity was associated with lower uptake in piriform cortex and higher uptake in ventral hippocampus, whereas during heroin seeking, addiction severity was associated with lower uptake in postsubiculum and cerebellum. Addiction severity was not associated with differences in social measures or FDG uptake during social-seeking. These findings identify brain metabolic features of heroin addiction vulnerability in a rat model that may serve as brain biomarkers of human opioid addiction.},

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pubstate = {published},

tppubtype = {article}

}