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PYY3-36 infused systemically or directly into the VTA attenuates fentanyl seeking in male rats.
Caffrey, A; Lavecchia, E; Merkel, R; Zhang, Y; Chichura, K S; Hayes, M R; Doyle, R P; Schmidt, H D.
Afiliación
  • Caffrey A; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Lavecchia E; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Merkel R; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Zhang Y; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Chichura KS; Department of Chemistry, Syracuse University, NY, 13244, USA.
  • Hayes MR; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Doyle RP; Department of Chemistry, Syracuse University, NY, 13244, USA; Departments of Medicine and Pharmacology, State University of New York, Upstate Medical University, Syracuse, NY, 13210, USA.
  • Schmidt HD; Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: hschmidt@nursing.upenn.edu.
Neuropharmacology ; 239: 109686, 2023 11 15.
Article en En | MEDLINE | ID: mdl-37572954
More effective treatments for fentanyl use disorder are urgently needed. An emerging literature indicates that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate voluntary opioid taking and seeking in rodents. However, GLP-1R agonists produce adverse malaise-like effects that may limit patient compliance. Recently, we developed a dual agonist of GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) that attenuates fentanyl taking and seeking at doses that do not produce malaise-like effects in opioid-experienced rats. Whether activating Y2Rs alone is sufficient to reduce opioid taking and seeking, however, is not known. Here, we investigated the efficacy of the Y2R ligand PYY3-36 to reduce fentanyl self-administration and the reinstatement of fentanyl-seeking behavior, a model of relapse in humans. Male rats were allowed to self-administer fentanyl (2.5 µg/kg, i.v.) for 21 days on a fixed-ratio 5 (FR5) schedule of reinforcement. Rats were then pretreated with vehicle or PYY3-36 (50 µg/kg s.c.; 0.1 and 1.0 µg/100 nL intra-VTA) prior to fentanyl self-administration test sessions. There were no effects of systemic or intra-VTA PYY3-36 on intravenous fentanyl self-administration. Opioid taking was then extinguished. Prior to subsequent reinstatement test sessions, rats were pretreated with vehicle or PYY3-36 (50 µg/kg s.c.; 0.1 and 1.0 µg/100 nL intra-VTA). Both systemic and intra-VTA administration of PYY3-36 attenuated fentanyl reinstatement in male rats at doses that did not affect food intake or produce adverse malaise-like effects. These findings indicate that Y2R agonism alone is sufficient to decrease fentanyl-seeking behavior during abstinence in opioid-experienced rats and further support strategies aimed at targeting Y2Rs for treating opioid use disorders.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fentanilo / Trastornos Relacionados con Opioides Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Neuropharmacology Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fentanilo / Trastornos Relacionados con Opioides Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Neuropharmacology Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido