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
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
Externí odkaz: