Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in MiceReportar como inadecuado




Differential Regulation of MAPK Phosphorylation in the Dorsal Hippocampus in Response to Prolonged Morphine Withdrawal-Induced Depressive-Like Symptoms in Mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Depression is one of the most frequent neuropsychiatric comorbidities associated with opiate addiction. Mitogen activated protein kinase MAPK and MAPK phosphatase MKP are involved in drug addiction and depression. However, the potential role of MAPK and MKP in depression caused by morphine withdrawal remains unclear. We utilized a mouse model of repeated morphine administration to examine the molecular mechanisms that contribute to prolonged withdrawal induced depressive-like behaviors. Depressive-like behaviors were significant at 1 week after withdrawal and worsened over time. Phospho-ERK extracellular signal-regulated protein kinase was decreased and MKP-1 was elevated in the hippocampus, and JNK c-Jun N-terminal protein kinase, p38 p38 protein kinase and MKP-3 were unaffected. A pharmacological blockade of MKP-1 by intra-hippocampal sanguinarine SA infusion prevented the development of depressive-like behaviors and resulted in relatively normal levels of MKP-1 and phospho-ERK after withdrawal. Our findings support the association between hippocampal MAPK phosphorylation and prolonged morphine withdrawal-induced depression, and emphasize the MKP-1 as an negative regulator of the ERK phosphorylation that contributes to depression.



Autor: Wei Jia , Rui Liu , Jianguo Shi, Bin Wu, Wei Dang, Ying Du, Qiong Zhou, Jianhua Wang, Rui Zhang

Fuente: http://plos.srce.hr/



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