Nature Neuroscience
August 30, 2022
Polymnia Georgiou, Panos Zanos, Ta-Chung M. Mou et al.
We show that the sex of human experimenters affects mouse behaviors and responses following administration of the rapid-acting antidepressant ketamine and its bioactive metabolite (2R,6R)-hydroxynorketamine. Mice showed aversion to the scent of male experimenters, preference for the scent of female experimenters and increased stress susceptibility when handled by male experimenters. This...
Journal of Clinical Investigation
November 19, 2019
Danielle M. Gerhard, Santosh Pothula, Rong-Jian Liu et al.
345 citations
A single sub-anesthetic dose of ketamine, an NMDA receptor (NMDAR) antagonist, produces rapid and sustained antidepressant actions in depressed patients, addressing a major unmet need for the treatment of mood disorders. Ketamine produces a rapid increase in extracellular glutamate and synaptic formation in the prefrontal cortex, but the initial cellular trigger that initiates these and its...
Nature Communications
June 3, 2019
Farhan Ali, Danielle M. Gerhard, Katherine Sweasy et al.
201 citations
A subanesthetic dose of ketamine causes acute psychotomimetic symptoms and sustained antidepressant effects. In prefrontal cortex, the prevailing disinhibition hypothesis posits that N-methyl-d-aspartate receptor (NMDAR) antagonists such as ketamine act preferentially on GABAergic neurons. However, cortical interneurons are heterogeneous. In particular, somatostatin-expressing (SST)...
American Journal of Psychiatry
January 4, 2019
Satoshi Deyama, Eunyoung Bang, Eric S. Wohleb et al.
100 citations
OBJECTIVE: -methyl-d-aspartate receptor antagonist ketamine produces rapid and sustained antidepressant actions even in patients with treatment-resistant depression. Vascular endothelial growth factor (VEGF) has been implicated in the effects of conventional monoamine-based antidepressants, but the role of VEGF in the rapid antidepressant actions of ketamine remains unclear. The authors...
Current Neuropharmacology
March 10, 2016
Eric S. Wohleb, Danielle M. Gerhard, Alex Thomas et al.
148 citations
Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs...
Drug Discovery Today
February 6, 2016
Danielle M. Gerhard, Eric S. Wohleb, Ronald S. Duman
Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the...