ECS-induced mossy fiber sprouting and BDNF expression are attenuated by ketamine pretreatment

Recent evidence suggests hippocampal and possibly cortical atrophy is assoc iated with major depression. Chronic electroconvulsive seizures (ECS) induc e brain-derived neurotrophic factor (BDNF) expression and sprouting of the mossy fiber pathway in the hippocampus, effects that may be related to elec troconvulsive therapy's (ECT) mechanism of action. The objective of this st udy was to investigate the role of NMDA (N-methyl-D-aspartate) receptor in mediating the ECS-induced mossy fiber sprouting and BDNF expression. Timm h istochemistry and in situ hybridization methodologies were used to determin e the effect of pretreatment with ketamine, an NMDA antagonist, on ECS-indu ced sprouting and BDNF expression. The results demonstrate the ability of k etamine pretreatment to attenuate ECS-induced sprouting in the dentate gyru s and BDNF expression in the medial prefrontal cortex and the dentate gyrus . In addition, we found a significant decrease in seizure duration with ket amine pretreatment. These data suggest that NMDA receptor activation contri butes to both the regulation of neurotrophic factor expression and the morp hological changes associated with seizure activity. However, other effects resulting from shortened seizure duration and seizure intensity cannot be e xcluded. These findings are of increasing interest, as they relate to the u se of ECT in the treatment of depression, and the specific anesthetic agent s that are used.