ArticleBrain sciences2026
Fentanyl Induces Behavioral Sensitization and Decreases Class IIa HDAC Expression-Activity in Brain as Measured by [
Article in Brain sciences, 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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Abstract
backgroundAlthough fentanyl significantly contributes to opioid-related morbidity and mortality, little is known about the epigenetic changes that may influence long-term neuronal adaptations.
objectiveThe effects of repeated fentanyl administration on class IIa histone deacetylase (HDAC) expression-activity were studied using the radiotracer [
methodsFemale and male Wistar rats received 14 days of fentanyl (20 μg/kg) or saline injections and a 14-day drug-free period followed by a single fentanyl or saline challenge dose on day 28. Locomotor activity (LMA) was measured on days 0, 1, 14, and 28 with PET imaging being performed at baseline and again on day 28 following the fentanyl/saline challenge and LMA. The percent change in standard uptake value (body weight corrected) between pre- and post-administration was calculated as a measure of class IIa HDAC expression-activity.
resultsRepeated fentanyl exposure resulted in significantly increased LMA in both sexes compared to controls. Females displayed an earlier onset (day 1) and a greater magnitude of behavioral sensitization on days 14 and 28 compared to males. Fentanyl significantly decreased class IIa HDAC expression-activity across time in the whole brain and in reward-related brain regions without sex differences.
conclusionsProlonged fentanyl exposure induces robust sex-specific locomotor sensitization with varying magnitude over time, suggesting differential neuroadaptive processes. Fentanyl also appears to induce epigenetic changes in the brain independent of sex and region. The effect of fentanyl on class II HDACs may not directly impact the expression of behavioral sensitization.
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