Sex-specific transcriptional signatures of oxycodone persist during withdrawal and abstinence in the suprachiasmatic nucleus of heterogeneous stock rats
Why this work is in the frame
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Bibliographic record
Abstract
Opioid use disorder (OUD) is a major public health problem. Sleep and circadian disruptions are recognized as hallmarks of substance use disorders, often emerging during withdrawal and lasting into abstinence. Little is known about the impact of opioids on the brain's primary circadian pacemaker, the suprachiasmatic nucleus (SCN). We examined SCN transcriptomic changes in genetically diverse heterogeneous stock rats across different opioid physiological and behavioral states (naïve, oxycodone intoxication, acute withdrawal, and prolonged abstinence), alongside behavioral assessments. In females, intoxication and withdrawal altered pathways related to neurotransmission, circadian rhythms, and inflammation, while in males, changes involved immune regulation and DNA damage. During abstinence, females showed enrichment in stress-related pathways, particularly those involved in energy metabolism and neurotransmitter function, whereas males exhibited enrichment in pathways related to cellular detoxification and oxidative stress, suggesting lasting, sex-specific effects during withdrawal and abstinence. The highest proportion of sex-specific rhythmic differentially expressed genes were identified during abstinence compared to other states. Co-expression network analysis identified a module linked to synaptic signaling and another linked to ciliary function, which were positively and negatively associated with intoxication, respectively. The genes in the synaptic signaling module were positively correlated with addiction-related behaviors during abstinence, while the genes in the ciliary module inversely correlated with these behaviors during intoxication, linking opioid-induced alterations in the SCN to addiction-like phenotypes. These findings highlight the SCN as a dynamic, sex-specific target of opioid exposure and suggest that SCN alterations may contribute to long-term behavioral and physiological consequences of OUD.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it