title: The activation of adenosine monophosphate-activated protein kinase in rat hippocampus contributes to the rapid antidepressant effect of ketamine.
abstract: Recent studies have shown a rapid, robust, and lasting antidepressant effect of ketamine that makes ketamine a promising antidepressant drug. However, the mechanisms underlying this rapid antidepressant effect remain incompletely understood. The goal of the present study was to determine whether adenosine monophosphate-activated protein kinase (AMPK) was involved in ketamine's rapid antidepressant effect during the forced swimming test (FST). In the first stage of experiment, a lower level of phosphorylated form of AMPK (p-AMPK) in the hippocampus and a longer immobility time were observed in the depressed rats during FST; whereas ketamine reversed these changes at 30min after the administration. In the second stage of experiment, we observed that, ketamine up-regulated the levels of p-AMPK and brain-derived neurotrophic factor (BDNF) in the hippocampus of the depressed rats. Moreover, AMPK agonist strengthened the antidepressant effect of ketamine with an up-regulation of BDNF, while AMPK antagonist attenuated the antidepressant effect of ketamine with a down-regulation of BDNF. In conclusion, our results suggest that the activation of AMPK in rat hippocampus is involved in the procedure of ketamine exerting rapid antidepressant effect through the up-regulation of BDNF.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Shi X
authors.initials: SX
authors.lastname: Xu
authors.forename: Zhi Q
authors.initials: ZQ
authors.lastname: Zhou
authors.forename: Xiao M
authors.initials: XM
authors.lastname: Li
authors.forename: Mu H
authors.initials: MH
authors.lastname: Ji
authors.forename: Guang F
authors.initials: GF
authors.lastname: Zhang
authors.forename: Jian J
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D007649:Ketamine; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide
keywords: Adenosine monophosphate-activated protein kinase; Depression; Hippocampus; Ketamine; Rat