{
  "abstract": "Schizophrenia and nicotine misuse comorbidity frequently emerges during adolescence. Although the dorsal striatum has received less attention than mesolimbic regions in this context, growing evidence supports its involvement in both schizophrenia-related dysfunction and the transition to compulsive drug-seeking. Here, we investigated dorsal striatal proteomic alterations in adolescent male and female C57BL/6 mice modeled to schizophrenia (phencyclidine: 2.5 mg/kg, s.c., 15 days) with a history of nicotine exposure (nicotine: 24 mg/kg/day, minipump infusions, 7 days). Dorsal striatum samples were analyzed by label-free quantitative proteomics, followed by Reactome pathway enrichment and interactome map analyses. Co-exposure induced sex-dependent alterations. Females exhibited greater proteomic disruption, whereas in males, co-exposure amplified phencyclidine-associated alterations while attenuating nicotine-driven effects. Across sexes, convergent enrichment was observed in pathways related to immune signaling, metabolic regulation and signal transduction. Female interactome analysis identified glyceraldehyde-3-phosphate dehydrogenase (Gapdh) as the most highly connected node linked to proteins involved in bioenergetics, RNA processing, and apoptosis, while the male network was centered on peptidyl-prolyl cis-trans isomerase (Fkbp1a) and associated with proteostasis-related processes. Our results identify the dorsal striatum as an emerging molecular target in an animal model combining schizophrenia-related and nicotine exposure-related insults and highlight pathways and candidate molecular markers to be further investigated and validated.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 Andar—Vila Isabel, Rio de Janeiro 20550-170, RJ, Brazil",
    "Departamento de Ciências Biomédicas e Saúde, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Cabo Frio 28905-320, RJ, Brazil",
    "Departamento de Ciências, Faculdade de Formação de Professores, Universidade do Estado do Rio de Janeiro (UERJ), São Gonçalo 24435-005, RJ, Brazil"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Thainá Pereira Souza",
      "orcid": "0000-0003-3081-6740"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrés Rodríguez-Vega",
      "orcid": "0000-0001-5875-7282"
    },
    {
      "affs": [
        1
      ],
      "name": "Ana Carolina Dutra-Tavares",
      "orcid": "0000-0001-9436-2712"
    },
    {
      "affs": [
        0
      ],
      "name": "Keila Alves Semeão",
      "orcid": "0000-0001-8702-6630"
    },
    {
      "affs": [
        0
      ],
      "name": "Claudio Carneiro Filgueiras",
      "orcid": "0000-0003-4522-4799"
    },
    {
      "affs": [
        2
      ],
      "name": "Anderson Ribeiro-Carvalho",
      "orcid": "0000-0003-4324-1413"
    },
    {
      "affs": [
        0
      ],
      "name": "Alex Christian Manhães",
      "orcid": "0000-0003-4629-8343"
    },
    {
      "affs": [
        0
      ],
      "name": "Yael Abreu-Villaça",
      "orcid": "0000-0002-9801-6179"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0k8krf0kcy6wq.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27209328",
  "fulltext_url": "https://europepmc.org/articles/PMC13705055",
  "id": "0k8krf0kcy6wq",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/20/9328",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2738|Schizophrenia research and treatment"
    ]
  ],
  "openalex": "W7223029489",
  "pdf_url": "https://europepmc.org/articles/PMC13705055?pdf=render",
  "pmcid": "PMC13705055",
  "pmid": "42942095",
  "published": "2026-10-20",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0k8krf0kcy6wq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27209328",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/20/9328"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42942095",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42942095"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Schizophrenia research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Beyond Classical Reward Circuits: Dorsal Striatum Proteomic Alterations in an Adolescent Phencyclidine-Induced Mouse Model of Schizophrenia and Nicotine Use",
  "title_text": "Beyond Classical Reward Circuits: Dorsal Striatum Proteomic Alterations in an Adolescent Phencyclidine-Induced Mouse Model of Schizophrenia and Nicotine Use",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:12Z",
  "url": "https://research.draconitic.com/paper/0k8krf0kcy6wq",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}