{
  "abstract": "Background and Purpose High novelty-seeking is an endophenotype associated with greater vulnerability to drug addiction, marked by a hyperdopaminergic state and reduced dopamine D2 receptor (D2R) levels in the dorsal striatum (DS). G protein-coupled receptor kinases (GRKs) regulate desensitization, internalization, and recycling of these receptors, including the D2R. This study investigated the relevance of GRK2 and 3 (GRK2/3) in novelty-seeking behavior and striatal dopamine dynamics. Experimental Approach Individual novelty-seeking trait was assessed in Sprague Dawley rats using an open-field test. D2R, GRK2, and GRK5 protein levels were measured in synaptosomal DS samples using Western Blot. Pharmacological inhibition of GRK2/3 was assessed using Cmpd101. We tested the effect of systemic Cmpd101 administration on contextual novelty discrimination and local Cmpd101 perfusion on baseline and stimulus-evoked extracellular dopamine (DA) levels in the DS. Key Results Locomotor activity in a novel environment inversely correlated with the synaptosomal GRK2 and D2R protein levels in the DS. Systemic Cmpd101 treatment modulated the locomotor discrimination index in a novelty phenotype-dependent manner. Moreover, local Cmpd101 perfusion in the DS elicited a sustained elevation in basal extracellular dopamine levels and significantly blunted subsequent stimulus-evoked DA release, both effects independent of novelty-seeking phenotype. Conclusion and Implications Together, our findings link GRK2/3 signaling to individual differences in novelty-seeking and striatal dopaminergic function. These results suggest a potential relevance to drug addiction vulnerability.",
  "abstract_shown": true,
  "affiliations": [
    "Universidad Arturo Prat"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "S. Davila"
    },
    {
      "name": "C. Starocelsky"
    },
    {
      "name": "C. Pino"
    },
    {
      "name": "F. Codocedo"
    },
    {
      "name": "C. Guzman-Munoz"
    },
    {
      "name": "B. Bossel"
    },
    {
      "name": "F. Novoa"
    },
    {
      "name": "M. Gonzalez"
    },
    {
      "name": "M. E. Andres"
    },
    {
      "affs": [
        0
      ],
      "name": "R. I. Gatica"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17pgac3xbm8qy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.753780",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753780v1.full",
  "id": "17pgac3xbm8qy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753780v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2804|Neurotransmitter Receptor Influence on Behavior"
    ]
  ],
  "openalex": "W7215081716",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753780v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/17pgac3xbm8qy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:42Z",
      "native_id": "10.64898/2026.09.25.753780",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753780v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Individual differences in novelty-seeking behavior are modulated by GRK2/3 inhibition in rats",
  "title_text": "Individual differences in novelty-seeking behavior are modulated by GRK2/3 inhibition in rats",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:42Z",
  "url": "https://research.draconitic.com/paper/17pgac3xbm8qy",
  "venue": "bioRxiv",
  "versions": []
}