Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway
Autor: | Beyza Ayazgök, Tomi Rantamäki, Elisabeth Waltisperger, Muris Humo, Léa J. Becker, Ipek Yalcin |
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Přispěvatelé: | Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hacettepe University = Hacettepe Üniversitesi, University of Helsinki, Drug Research Program, Division of Pharmacology and Pharmacotherapy, Laboratory of Neurotherapeutics, SLEEPWELL Research Program |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
Time Factors Neuropathic pain-induced depression [SDV]Life Sciences [q-bio] Comorbidity Pharmacology ACTIVATION Mice pERK 0302 clinical medicine NMDA RECEPTOR BLOCKADE RAT MODEL Medicine Depression (differential diagnoses) Pain Measurement Depression NEUROPATHIC PAIN Chronic pain Antidepressive Agents 3. Good health anterior cingulate cortex 317 Pharmacy Neuropathic pain Systemic administration NMDA receptor Ketamine [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Chronic Pain PHARMACOLOGICAL-TREATMENT medicine.drug EXPRESSION MAP Kinase Signaling System BEHAVIORS MECHANISMS Anterior cingulate ACC 03 medical and health sciences Animals Biological Psychiatry PROTEIN-KINASE PHOSPHATASE-1 MKP-1 business.industry 3112 Neurosciences Antagonist medicine.disease 030227 psychiatry Mice Inbred C57BL Mood disorders business |
Zdroj: | Progress in Neuro-Psychopharmacology and Biological Psychiatry Progress in Neuro-Psychopharmacology and Biological Psychiatry, Elsevier, 2020, 100, pp.109898. ⟨10.1016/j.pnpbp.2020.109898⟩ |
ISSN: | 0278-5846 |
Popis: | International audience; Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socioeconomic burden and result in disability affecting millions individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, is shown to be efficient in treating both pain and depression-related symptoms. However, the molecular characteristics of its role in chronic pain-induced depression remain largely unexplored. Hence, we studied the behavioral and molecular effects of a single systemic administration of ketamine (15 mg/kg, i.p.) on mechanical hypersensitivity and depressive-like consequences of chronic neuropathic pain. We showed that ketamine transiently alleviated mechanical hypersensitivity (lasting < 24h), while its antidepressant effect was observed even 72 hours after administration. In addition, ketamine normalized the upregulated expression of the mitogen activated protein kinase (MAPK) phosphatase 1 (MKP-1) and the downregulated phosphorylation of extracellular signal-regulated kinase (pERK) in the anterior cingulate cortex (ACC) of mice displaying neuropathic pain-induced depressive-like behaviors. This effect of ketamine on the MKP-1 was first detected 30 minutes after the ketamine administration and persisted until 72h. Altogether, these findings provide insights into the behavioral and molecular changes associated with single ketamine administration in the comorbidity of chronic pain and depression. |
Databáze: | OpenAIRE |
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