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Apremilast reduces co-occurring alcohol drinking and mechanical allodynia and regulates central amygdala GABAergic transmission
Valentina Vozella, … , Michal Bajo, Marisa Roberto
Valentina Vozella, … , Michal Bajo, Marisa Roberto
Published April 22, 2025
Citation Information: JCI Insight. 2025;10(8):e189732. https://doi.org/10.1172/jci.insight.189732.
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Research Article Neuroscience Public Health

Apremilast reduces co-occurring alcohol drinking and mechanical allodynia and regulates central amygdala GABAergic transmission

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Abstract

The FDA-approved phosphodiesterase type 4 (PDE4) inhibitor, apremilast, has been recently investigated as a pharmacotherapy for alcohol use disorder (AUD) with promising efficacy in rodent models and humans. However, apremilast’s effects on mechanical allodynia associated with AUD as well as distinct responses of this drug between males and females are understudied. The present study examined the behavioral and electrophysiological effects of apremilast in Marchigian Sardinian alcohol-preferring (msP) rats and their Wistar counterparts. We used a 2–bottle choice (2-BC) alcohol drinking procedure and tested mechanical sensitivity across our drinking regimen. Spontaneous inhibitory GABA-mediated postsynaptic currents from the central nucleus of the amygdala (CeA) following apremilast application were tested in a subset of rats using ex vivo electrophysiology. Transcript levels for Pde4a or -4b subtypes were assessed for their modulation by alcohol. Apremilast reduced alcohol drinking in both strains of rats. Apremilast reduced mechanical allodynia immediately after drinking, persisting into early and late abstinence. Apremilast increased GABAergic transmission in CeA slices of alcohol-exposed Wistars but not msP rats, suggesting neuroadaptations in msPs by excessive drinking and mechanical allodynia. Pde4 subtype transcript levels were increased in CeA by alcohol. These results suggest that apremilast alleviates co-occurring excessive drinking and pain sensitivity, and they further confirm PDE4’s role in pain-associated AUD.

Authors

Valentina Vozella, Vittoria Borgonetti, Bryan Cruz, Celsey M. St. Onge, Ryan Bullard, Roman Vlkolinsky, Diego Gomez Ceballos, Angela R. Ozburn, Amanda J. Roberts, Roberto Ciccocioppo, Michal Bajo, Marisa Roberto

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Usage data is cumulative from April 2025 through December 2025.

Usage JCI PMC
Text version 2,125 244
PDF 359 38
Figure 806 1
Table 76 0
Supplemental data 152 13
Citation downloads 180 0
Totals 3,698 296
Total Views 3,994

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