Antidepressant-like effects of ketamine in a mouse model of serotonergic dysfunction

Abstract

Traditional monoaminergic treatments of depression frequently exhibit suboptimal tolerability and effectiveness. The ‘short’ (s) allele variant of 5-HTTLPR is known to compromise transcriptional efficacy of the serotonin transporter (5-HTT) and can reduce treatment response to traditional antidepressants (e.g. selective serotonin reuptake inhibitors or SSRIs). This study sought to establish the 5-HTT knock-out (KO) line as a mouse model of SSRI-resistant depression and assess its response to a novel glutamatergic antidepressant, ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist. Following acute antidepressant treatment, 5-HTT KO mice and wild-type (WT) controls wer..