Molecular profile of dissociative drug ketamine in relation to its rapid antidepressant action.

ABSTRACT: The NMDA receptor antagonist ketamine was found to act as a fast-acting antidepressant. The effects of single treatment were reported to persist for days to weeks, even in otherwise treatment-refractory cases. Identification of the mechanisms underlying ketamine's antidepressant action may permit development of novel drugs, with similar clinical properties but lacking psychotomimetic, sedative and other side effects.We applied whole-genome microarray profiling to analyze detailed time-course (1, 2, 4 and 8 h) of transcriptome alterations in the striatum and hippocampus following acute administration of ketamine, memantine and phencyclidine in C57BL/6 J mice. The transcriptional effects of ketamine were further analyzed using next-generation sequencing and quantitative PCR. Gene expression alterations induced by the NMDA antagonists were compared to the molecular profiles of psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids.We identified 52 transcripts (e.g. Dusp1, Per1 and Fkbp5) with altered expression (FDR?

SUBMITTER: Ficek J 

PROVIDER: S-EPMC4869301 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature