Publications by authors named "Konrad R Dabrowski"

Recent progress in psychiatric research has highlighted neuroinflammation in the pathophysiology of opioid use disorder (OUD), suggesting that heightened immune responses in the brain may exacerbate opioid-related mechanisms. However, the molecular mechanisms resulting from neuroinflammation that impact opioid-induced behaviors and transcriptional pathways remain poorly understood. In this study, we have begun to address this critical knowledge gap by exploring the intersection between neuroinflammation and exposure to the opioid heroin, utilizing lipopolysaccharide (LPS)-induced neuroinflammation, to investigate transcriptional changes in the nucleus accumbens (NAc), an essential region in the mesolimbic dopamine system that mediates opioid reward.

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Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HTR), a well-documented target for modulation of drug seeking, and evidence suggests 5-HTR agonists may dampen motivation for opioids.

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Preclinical and human studies indicate psilocybin may reduce perseverant maladaptive behaviors, including nicotine and alcohol seeking. Such studies in the opioid field are lacking, though opioids are involved in more >50% of overdose deaths. Psilocybin is an agonist at the serotonin 2A receptor (5-HTR), a well-documented target for modulation of drug seeking, and evidence suggests 5-HTR agonists may dampen motivation for opioids.

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Opioid overdose is the leading cause of accidental death in the United States and remains a major public health concern, despite significant resources aimed at combating opioid misuse. Neurobiological research to elucidate molecular and cellular consequences of opioid exposure is required to define avenues to explore for reversal of opioid-induced neuroadaptations. Opioids impart well-documented regulation of the transcriptome and epigenetic modifications in the brain, but opioid-induced epitranscriptomic posttranscriptional regulation of RNA is vastly understudied.

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Article Synopsis
  • The orbitofrontal cortex (OFC) is crucial for reward-seeking behavior but its related molecular mechanisms, particularly involving circular RNAs (circRNAs), are not well understood.
  • A study identified 92 circRNAs in the OFC influenced by sucrose self-administration, notably showing downregulation of circNrxn3, which is linked to synaptogenesis, learning, and memory.
  • Knock-down experiments of circNrxn3 revealed its role in increasing sucrose motivation and self-administration while affecting gene regulation and splicing, indicating it’s the first known circRNA to regulate reward behavior through interactions with the splicing factor SAM68.
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Article Synopsis
  • * A study investigated how heroin affects circular RNAs (circRNAs) in the orbitofrontal cortex (OFC) of rats, identifying 76 circRNAs that changed significantly after heroin self-administration.
  • * The research highlights specific circRNAs linked to heroin exposure, suggesting they may influence neurobiological changes related to addiction by interacting with microRNAs and affecting cellular processes.
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