When the brain loses TrkBactivation : The effects of ketamine on BDNF-TrkB neurotransmission in animal models of depression

Abstract: Ketamine is a non-competitive N-methyl-D-aspartate (NMDA)-channel blocker that has recently shown promise in the treatment of major depressive disorder, distinguishing itself from classical anti-depressants through its rapid and lasting effects when given at sub-anaesthetic doses. Animal models of depression are commonly used to research individual mechanisms of action and this literature review aimed to investigate how ketamine influences BDNF-TrkB neurotransmission in the hippocampus and prefrontal cortex within animal models of depression. Reduced levels of BDNF and TrkB-transmission, as well as downstream signalling, are common in both humans experiencing depression and in rodent models of depression, and ketamine was found to counteract this reduction in the majority of studies reviewed. In the majority of studies ketamine’s anti-depressant actions were viewed to be at least partially connected to its effects on BDNF-TrkB neurotransmission. This was supported by the anti-depressant effects being readily blocked by pharmacological inhibition of TrkB. Inhibition also blocked the downstream neurobiological changes associated with ketamines anti-depressant effects.