Glutamate and the Neural Basis of the Subjective Effects of Ketamine
Archives of General Psychiatry February 1, 2008 J.f.w. Deakin, Jane Lees, Shane Mckie et al. 315 citations
Ketamine, which blocks NMDA glutamate receptors and secondarily increases glutamate release, produces psychosis-like symptoms. Using fMRI, a double-blind crossover study with 33 healthy men found that ketamine caused a rapid decrease in ventromedial frontal cortex activity that predicted dissociative effects, and increased activity in posterior cingulate, thalamus, and temporal regions that correlated with psychosis scores. Pretreatment with lamotrigine, a glutamate release inhibitor, prevented many brain changes and symptoms. The findings suggest ketamine's effects involve increased glutamate release and may model two core psychosis processes: abnormal perceptions and impaired cognitive-emotional evaluation.