Ketamine induces rapid and sustained antidepressant-like effects in chronic pain induced depression: Role of MAPK signaling pathway.

Progress in Neuro-psychopharmacology & Biological Psychiatry
Muris HumoIpek Yalcin

Abstract

Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions of 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 <24 h), while its antidepressant effect was observed even 72 h 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...Continue Reading

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Citations

Feb 11, 2021·Chemical Research in Toxicology·Bonnie RobinsonJyotshna Kanungo
Apr 27, 2021·Frontiers in Psychiatry·Shengtao YangAmy F T Arnsten
May 6, 2021·Neuroscience and Biobehavioral Reviews·Sakina J RizviTim Salomons
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Nov 28, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shogo SatoRicardo Orozco-Solis

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