{
  "abstract": "The consumption of energy drinks with high concentrations of caffeine is increasing among adolescents and young adults. Caffeine is a central nervous system stimulant that acts as a non-selective antagonist of adenosine receptors. Adenosine receptor signalling is involved in several processes in the brain, but the role it plays in caffeine-induced effects on developing neuronal cells is poorly understood. This study investigates how caffeine, the selective adenosine A2a receptor antagonist istradefylline and the adenosine A2a receptor agonist CGS21680 affect cell viability, neurite outgrowth, branching and mRNA expression in immature primary rat cortical and hippocampal cell cultures. Caffeine significantly decreased the number of branches, junctions and endpoints in both hippocampal and cortical cells, with the effect appearing to be more potent in hippocampal cells. In addition, high concentrations of caffeine decreased neurite length and mitochondrial function in both hippocampal and cortical cells, as well as decreasing MAO-B and tryptophan hydroxylase 2 expression in cortical cells. Istradefylline also decreased neurite branching and outgrowth in hippocampal cells, although these effects were less pronounced than those observed with caffeine. These findings indicate that caffeine reduces neuronal branching and that high caffeine concentrations also reduce neurite length and mitochondrial activity and affect genes involved in monoaminergic signalling and neuronal function in developing neuronal cells. These findings may be relevant to understanding the cellular consequences of high caffeine exposure during brain development.",
  "abstract_shown": true,
  "affiliations": [
    "Neuropharmacology and Biological Addiction Research, Department of Pharmaceutical Biosciences, Uppsala University, Sweden."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sara Florén Lind Bjurling"
    },
    {
      "affs": [
        0
      ],
      "name": "Frida Stam"
    },
    {
      "affs": [
        0
      ],
      "name": "Erik Nylander"
    },
    {
      "affs": [
        0
      ],
      "name": "Alfhild Grönbladh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9n3s7j2kw6w91.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ibneur.2026.10.002",
  "fulltext_url": "https://europepmc.org/articles/PMC13740863",
  "id": "9n3s7j2kw6w91",
  "issns": [
    "2667-2421"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997023",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Coffee research and impacts"
    ]
  ],
  "openalex": "W7221322249",
  "pdf_url": "https://europepmc.org/articles/PMC13740863?pdf=render",
  "pmcid": "PMC13740863",
  "pmid": "42997023",
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9n3s7j2kw6w91.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42997023",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997023"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Coffee research and impacts",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "High-dose caffeine reduces neurite branching and alters expression of selected genes in immature primary rat cortical and hippocampal cell cultures.",
  "title_text": "High-dose caffeine reduces neurite branching and alters expression of selected genes in immature primary rat cortical and hippocampal cell cultures.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/9n3s7j2kw6w91",
  "venue": "IBRO neuroscience reports",
  "versions": []
}