Introduction
schizophrenia-like, treatment-resistant, depressive symptoms
The NMDA receptor antagonist ketamine not only transiently induces schizophrenia-like positive and cognitive symptoms, but also rapidly reduces depressive symptoms in otherwise treatment-resistant patients [During acute administration, ketamine was shown to have an immediate effect on CBF with increases in prefrontal and cingulate cortices, as well as in subcortical regions such as thalamus [Complementary insights into ketamine’s mechanism of action might be provided by direct modulatory approaches. Accordingly, several studies have demonstrated that effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, a broad-spectrum anticonvulsant that inhibits voltage-gated ion channels, with downstream effects resulting in inhibition of glutamate release [However, previous studies investigating the impact of lamotrigine pretreatment were conducted during the acute administration of ketamine and it is not yet known whether the inhibition of glutamate release via lamotrigine has longer term consequences. Along that line, previous studies investigating the impact of ketamine on perfusion were conducted either during or after its administration, but no study has yet investigated both acute and delayed effects in the same participants. Longitudinal assessments of participants would however provide additional insights, given that psychotomimetic effects appear during the administration and quickly diminish, while antidepressant effects of ketamine are most pronounced 24 h after administration, thereby indicating sustained adaptive changes in brain dynamics [Consequently, the aim of the present study was to investigate acute and delayed (24 h) effects of a single dose of ketamine on resting brain perfusion in predefined brain regions. To determine whether these are modulated by inhibited glutamate release, we also investigated the impact of lamotrigine prior to ketamine administration.