Sex differences in the temporal neuromolecular and synaptogenic effects of the rapid-acting antidepressant drug ketamine in the mouse brain

Publication date: Available online 8 December 2018Source: NeuroscienceAuthor(s): Connor Thelen, Emily Flaherty, Joseph Saurine, Jonathon Sens, Sara Mohamed, Pothitos M. PitychoutisAbstractPreclinical evidence suggests that ketamine’s rapid and sustained antidepressant actions are due to the induction of synaptogenesis in the medial prefrontal cortex (mPFC) and the hippocampus (HIPP), two brain regions implicated in the pathophysiology of major depression. However, research on the neurobiological effects of ketamine has focused almost exclusively on males. Findings from our group and others indicate that female rodents are more reactive to ketamine’s antidepressant effects, since they respond to lower doses in antidepressant-predictive behavioral models. The sex-dependent mechanisms that mediate the antidepressant effects of ketamine in the female brain are elusive. Herein, we assessed the neurobiological effects of a single ketamine dose (10mg/kg; previously shown to induce rapid and sustained antidepressant-like effects in mice of both sexes), on glutamate release in the mPFC, as well as on the expression of synaptic plasticity markers, and spine density in the mPFC and the HIPP of C57BL/6J mice. Our data revealed that ketamine induced a sex-specific “glutamate burst” in the male mPFC. Ketamine activated the mammalian target of rapamycin complex 1 (mTORC1) pathway, induced rapid and sustained synaptic protein synthesis, and enhanced spine formation in the male mPFC o...
Source: Neuroscience - Category: Neuroscience Source Type: research