BDNF Release Is Required for the Behavioral Actions of Ketamine
The International Journal of Neuropsychopharmacology October 31, 2014 A. E. Lepack, M. Fuchikami, J. M. Dwyer et al. 369 citations
Ketamine's rapid antidepressant effects depend on the release of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC), which is triggered by activation of L-type voltage-dependent calcium channels (VDCCs). Infusing a neutralizing BDNF antibody into the mPFC blocked ketamine's behavioral effects in the forced swim test. Pretreatment with either nifedipine or verapamil, two different L-type calcium channel antagonists, also blocked these effects. In primary cortical neurons, ketamine stimulated BDNF release, and this release was prevented by inhibiting AMPA receptors or L-type VDCCs. The findings indicate that L-type VDCC activation and BDNF release mediate ketamine's antidepressant actions.