{
  "id": 6097767,
  "title": "Ketamine Modulates Endogenous Opioid Peptide Signaling and Reduces Heroin-Seeking in Male Long-Evans Rats",
  "url": "https://urgent.news/2026/09/06/ketamine-modulates-endogenous-opioid-peptide-signaling-and-reduces",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-06T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748554v1?rss=1"
  },
  "original_language": "en",
  "account": "Opioid Use Disorder (OUD) remains a significant public health concern, characterized by high relapse rates and limited treatment alternatives. Ketamine, a non-competitive N-Methyl-D-Aspartate receptor (NMDAR) antagonist, has shown promise in treating various psychiatric disorders due to its strong antidepressant effects and glutamate-mediated synaptic plasticity. However, the precise mechanisms of ketamine's therapeutic action are still unclear, with recent findings pointing towards its impact on the endogenous opioid system. Few studies have explored the potential of ketamine as a means to combat OUD. Hence, this investigation aimed to evaluate ketamine's capacity to rewire endogenous opioid and glutamatergic circuitry and diminish heroin-seeking behavior in male Long-Evans rats. Employing a multi-cohort design, the study examined ketamine's impacts on opioid-related gene expression, protein levels, and signaling pathways in critical brain areas linked to reward and addiction, followed by its effects on heroin-seeking behavior using a self-administration method. To delve into the mechanisms of plasticity, the researchers measured changes in the transcription of NMDAR subunits. The molecular data revealed heightened expression of genes and peptides involved in the endogenous opioid system at the protein level, increased mu-opioid receptor protein quantities, and heightened G protein activation, indicating heightened receptor functionality. More importantly, the transcriptional modifications were especially pronounced in the shell subregion of the nucleus accumbens (NAc). The study also uncovered that ketamine affected NMDAR subunit expression in the medial prefrontal cortex and NAc, implying alterations at the circuit level. Behavioral assessments showed that ketamine notably reduced heroin-primed, yet not cue-induced, seeking behavior. Overall, these findings propose that ketamine mitigates acute relapse susceptibility to opioids by synchronously modulating opioid and glutamatergic systems, suggesting its potential as a novel treatment for OUD.",
  "summary": "Opioid Use Disorder (OUD) continues to be a pressing public health crisis, marked by high relapse rates and limited treatment options. Ketamine, a non-competitive N-Methyl-D-Aspartate receptor (NMDAR) antagonist, has emerged as a promising therapeutic for numerous psychiatric illnesses due to its robust antidepressant properties and glutamate-mediated synaptic plasticity. However, ketamine's…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}